Dairy herd management practices that impact nitrogen utilization efficiency.

Improving the efficiency of feed N utilization by dairy cattle is the most effective means to reduce nutrient losses from dairy farms. The objectives of this study were to quantify the impact of different management strategies on the efficiency of feed N utilization for dairy farms in the Chesapeake Bay Drainage Basin. A confidential mail survey was completed in December 1998 by 454 dairy farmers in PA, MD, VA, WV, and DE. Nitrogen intake, urinary and fecal N, and efficiency of feed N utilization was estimated from survey data and milk analysis for each herd. Average efficiency of feed N utilization for milk production by lactating dairy cows (N in milk/N in feed x 100) was 28.4% (SD = 3.9). On average, farmers fed 6.6% more N than recommended by the National Research Council, resulting in a 16% increase in urinary N and a 2.7% increase in fecal N. Use of monthly milk yield and component testing, administration of bovine somatotropin (bST), and extending photoperiod with artificial light each increased efficiency of feed N utilization by 4.2 to 6.9%, while use of a complete feed decreased efficiency by 5.6%. Increased frequency of ration balancing and more frequent forage nutrient testing were associated with higher milk production, but not increased N utilization efficiency. Feeding protein closer to recommendations and increasing production per cow both contributed to improving efficiency of feed N utilization.

Use of milk urea nitrogen to improve dairy cow diets.

The hypothesis of this field study was that providing farmers with information regarding their herd's milk urea nitrogen (MUN) would result in more accurate feed management and a change in MUN toward target values. All dairy herd bulk tanks (n = 1156) in the Maryland and Virginia Milk Producers' Cooperative were tested for MUN each month for six months ending in May 1999. Farmers (n = 454) who returned a survey were provided with the results of their MUN analysis each month along with interpretive information. Survey results indicated that most (89.5%) dairy farmers did not routinely use MUN prior to participating in the project, but most (88%) extension agents and nutritionists in the region recommended it. The average MUN across all farms in the study increased in the spring, but the increase was 0.52 mg/dl lower for farmers receiving MUN results than for those who did not participate in the program. Farmers who indicated they increased dietary crude protein (CP) due to low MUN started with MUN values that were 3 mg/dl below target but ended with target values. Farmers who indicated that they decreased CP due to high MUN began the project with high MUN but decreased it by 1 mg/dl compared to non-participating farmers. At the end of the project, 30% of farmers responding to a follow-up survey indicated they would use MUN analysis in the future. Providing MUN results and interpretive information to farmers was documented to change feeding practices and subsequent MUN results.

Yohimbine use in a natural setting: effects on posttraumatic stress disorder.

BACKGROUND: Numerous laboratory-based studies have shown that chronic posttraumatic stress disorder (PTSD) is associated with alterations in catecholamines. In a recent neuroendocrine challenge study, IV yohimbine caused exaggerated subjective, behavioral, cardiovascular and catecholamine responses among combat veterans with PTSD compared to healthy controls. Yohimbine is an alpha-2-adrenergic receptor antagonist that activates noradrenergic neurons. METHODS: This report describes the experience of 4 individuals with PTSD who took over-the-counter oral yohimbine that they had purchased from a health food store or pharmacy. RESULTS: All 4 subjects experienced a marked exacerbation of anxiety/panic and PTSD-specific symptoms immediately after ingesting yohimbine in a natural setting. CONCLUSIONS: The response in these individuals closely resembled the response observed after IV yohimbine in combat veterans with PTSD. The present cases occurred in a natural setting and thus complement laboratory-based findings. The authors caution against the recreational or medical use of yohimbine in individuals who have PTSD.

Standardizing the expression and nomenclature of cancer treatment regimens. American Society of Health-System Pharmacist (ASHP), American Medical Association (AMA), American Nurses Association (ANA).

Guidelines for describing cancer chemotherapy regimens in all aspects of drug development, including treatment protocols, order forms, and product labels, are proposed. To complement the approaches to reducing medication errors that have been recommended by ASHP and others, pharmacists at the National Institutes of Health and the National Cancer Institute, with the input of oncology pharmacists from diverse areas of practice, developed guidelines for expressing chemotherapy dosage schedules and treatment regimens. The guidelines present standards that are broadly applicable and can be adopted by other institutions. Clear and unambiguous expression of all medication orders and consistency of treatment descriptions are suggested. Written treatment plans and orders should contain enough information to allow health care providers from diverse disciplines to compare them with published treatment descriptions and investigational protocols and must therefore include planned dosages and schedules expressed in patient-specific units. In general, drug dosages should be expressed as the amount of drug administered from a single container. When ordering drugs that are part of complex or combination-drug regimens, prescribers should write as many of the orders at one time as is possible, so that continuity might be preserved. Standard rules are proposed for describing chemotherapy regimens.

Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials.

BACKGROUND: The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. PURPOSE: Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. METHODS: During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups: birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. RESULTS: Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. CONCLUSIONS: Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. IMPLICATIONS: This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.

Expression of nerve-muscle topography during development.

Previous studies have indicated that in 2 muscles of the adult rat, the anterior serratus and the diaphragm, the rostrocaudal axis of the motoneuron pool projects topographically onto the rostrocaudal axis of the muscle. In the present work we have asked whether this orderly topography emerges as a function of postnatal synaptic rearrangement or whether this pattern is already established at birth. The anterior serratus muscle was studied over the period ranging from embryonic day 17 through postnatal day 30. Using 2 criteria of topography, average segmental innervation and average target field of cervical roots C6 and C7, we found that a topographic distribution of the motoneuron pool is already present prior to birth and maintained throughout the postnatal period. Moreover, both C6 and C7 form an orderly map over the surface of the serratus in the embryo, and the topography is sharpened during postnatal periods. The diaphragm also is topographically innervated at birth and undergoes a comparable sharpening of the projection map postnatally. We conclude that the topographic projection of motoneurons is established prior to birth in these muscles, and postnatal synaptic rearrangement serves to sharpen the topographic map toward the adult pattern. These results also suggest that the pursuit of basic mechanisms underlying topography should be directed toward initial embryonic nerve-muscle contacts.

Antihypertensive effects of 12 beta adrenoceptor antagonists in conscious spontaneously hypertensive rats: relationship to changes in plasma renin activity, heart rate and sympathetic nerve function.

Twelve beta adrenoceptor antagonists were examined for their effects on mean blood pressure (MBP), heart rate (HR), plasma renin activity (PRA) and sympathetic nerve function in spontaneously hypertensive rats (SHR). The selected drugs included cardioselective agents (acebutolol, atenolol and metoprolol), agents with intrinsic sympathomimetic activity (oxprenolol, acebutolol, alprenolol and pindolol) and agents with local anesthetic activity (propranolol, oxprenolol, acebutolol, alprenolol and labetalol). All 12 beta adrenoceptor antagonists, administered once daily for 4 days (30 mg/kg p.o.), significantly decreased MBP of SHR. This reduction in MBP was dissociable from both reductions in HR as well as peripheral beta adrenoceptor blockade. In addition, the onset of MBP reduction was slower than the onset of beta adrenoceptor blockade and became greater with duration of treatment. PRA activity was significantly and markedly reduced by both bunolol and metoprolol shortly after dosing at a time when HR was significantly reduced but MBP was not. Conversely, at a time when MBP was significantly reduced by both bunolol and metoprolol, PRA and HR were found to be normal. The changes in HR and PRA were correlated with peripheral beta adrenoceptor blockade but changes in MBP were not. Bunolol, metoprolol and propranolol had no consistent inhibitory effect on pressor responses to nerve stimulation in pithed SHR, although positive chronotropic responses to norepinephrine, tyramine, dimethylphenylpiperazinium and angiotensin I and II were significantly and markedly reduced. It is concluded that beta adrenoceptor antagonists, as a class, reduce MBP of conscious SHR, provided that sufficient time is allowed for this observation to occur. Furthermore, the reduction in MBP caused by beta adrenoceptor antagonists is unrelated to acute beta adrenoceptor blockade, changes in HR, reductions in PRA or inhibition of sympathetic nerve function. Finally, cardioselectivity, intrinsic sympathomimetric activity and local anesthetic activity are not required for the antihypertensive activity of these agents.

The effect of short-term obstruction on urinary bladder function in the rabbit.

The effect of short term partial obstruction on urinary bladder function was studied in rabbits. After 1 week of partial bladder obstruction, the bladders were significantly hypertrophied with a mass over 9 times that of control bladders. The obstruction resulted in a marked decrease in both intracellular ATP and muscarinic receptor density. In vitro response of isolated smooth muscle strips from the obstructed bladder body to cholinergic stimulation was only 50 per cent of the response of control bladders. The obstructed bladder was able to expel only 28 per cent of its volume whereas control bladders expelled 100 per cent of their volume. The results of these studies demonstrate the rapid nature of the response of the bladder to chronic obstruction. Within 1 week frank hypertrophy and significant defects in the contractile ability of the bladder were evident.

Metabolic and contractile effects of anoxia on the rabbit urinary bladder.

The in vitro metabolic and contractile effects of anoxia and glucose deprivation on the rabbit urinary bladder were studied. The exposure of isolated strips of rabbit urinary bladder to a glucose deficient medium equilibrated with nitrogen rather than with oxygen resulted in 1) a rapid decrease in baseline tension, 2) a progressive decrease in the intracellular concentration of adenosine 5'-triphosphate (ATP) and progressive increases in the concentrations of adenosine 5'-monophosphate and adenosine 5'-diphosphate, 3) a rapid decrease in the ability of bethanechol to stimulate contractility, and 4) the inability of bethanechol to maintain a sustained increase in contractile force. Recovery from a 60-minute exposure of bladder strips to anoxia was characterized by a rapid recovery of the ability of the bladder to respond to bethanechol (50 per cent recovery occurring within 15 minutes) and a slightly slower recovery of the intracellular ATP level. Both the contractile response to bethanechol and the intracellular concentration of ATP returned to control levels within 60 minutes after the termination of anoxia.

Species specificity of the platelet responses to 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine.

A semi-synthetic 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC) was shown to be highly species selective in its capacity to cause platelet aggregation and serotonin release. No effects were elicited on the rat or mouse platelets while platelets from human, dog, cat, rabbit, guinea pig and horse were highly sensitive to alkylacetyl-GPC. The hypotensive activity in the rat was not associated with thrombocytopenia. Preliminary evidence suggested that the inability of platelets of the rat and mouse to respond to alkylacetyl-GPC was not due to a difference in plasma inactivation of the substance but due to a difference in platelet responsiveness per se. The data also support the concept that the potent hypotensive property of this substance readily observed in the rat, is a result of an effect which is platelet-independent.

Clinical pharmacy in an emergency medicine setting.

A decentralized emergency medicine clinical pharmacy program was initiated and has operated now for over 1 year. The program attempted to answer two questions: is there a viable clinical pharmacy role in emergency medicine, and could staff pharmacists successfully function in such a role without formal clinical training and experience? Initial primary objectives were to provide an on-the-spot pharmaceutical consultation service and to initiate new or expanded traditional pharmacy support to staff and patients. A secondary objective was to provide expanded outpatient prescription service to emergency room patients.

Contribution of the kidneys but not adrenal glands to the acute antihypertensive effects of captopril in spontaneously hypertensive rats.

1. Captopril (100 mg/kg, orally) decreased blood pressure in spontaneously hypertensive (SH) rats. 2. Bilateral adrenalectomy either before or after captopril administration did not alter the antihypertensive effect of captopril. 3. Bilateral nephrectomy reversed the established antihypertensive effect of captopril and prevented any change in blood pressure to a subsequent dose of captopril. 4. It is concluded that kidneys but not adrenal glands are essential to the antihypertensive actions of captopril in SH rats.

Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats.

The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.

Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs.

Oral administration of SQ 14,225 (0.03--3 mg/kg) to conscious normotensive dogs caused inhibition of the pressor response to intravenously administered angiotensin I (AI), the duration of which was dose-dependent. All doses of 0.1 mg/kg or greater caused 85--95% inhibition 30 min after administration whereas 0.03 mg/kg produced only a 25% inhibition. Pressor responses to angiotensin II (AII) were not similarly inhibited. Blood pressure was moderately reduced in a dose-related manner and followed the same pattern as inhibition of the AI pressor responses. The maximum change occurred after 1.0 mg/kg with only a more rapid onset occurring after the 3.0 mg/kg dose. Heart rate was not appreciably changed. SQ 14,225 also increased plasma renin activity (PRA), the levels and duration of which were dose-related. These data indicate that SQ 14,225 is an orally effective, potent inhibitor of angiotensin I-converting enzyme (ACE) in dogs. It appears that in mongrel dogs, ACE inhibition results in a slight to moderate reduction in blood pressure and an increase in PRA.

Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme.

SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) markedly lowered the blood pressure of the renin-dependent aortic-ligated and two-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the one-kidney Goldblatt hypertensive rat. In the two-kidney Goldblatt rat, SQ 14,225 (p.o.) was about 10 times as potent as teprotide, the nonapeptide SQ 20,881 (s.c.). Oral doses of SQ 14,225 moderately reduced the blood pressure of the Wistar-Kyoto spontaneously hypertensive rat but not that of the normotensive Wistar-Kyoto rat. Bilateral nephrectomy abolished the antihypertensive activity of SQ 14,225 in the spontaneously hypertensive rat. SQ 14,225 and SQ 20,881 elicited parallel dose-response curves in the two-kidney renal hypertensive rat. Post-treatment of spontaneously hypertensive rats with either agent failed to augment the antihypertensive effect produced by effective doses of the other agent. The results suggest that SQ 14,225 acts primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension.

Regulation of nitrogen catabolic enzymes in chick liver -- effects of amino acids.

It is well-known that in the chick, dietary protein increases the levels of several hepatic enzymes that are involved in nitrogen metabolism and excretion. However, the biochemical mechanism of this response is essentially unknown. The experiments presented in this paper show that the chick is responding to alpha-amino nitrogen and not to any specific amino acid. Furthermore, it is shown that this system responds to endogenous sources of nitrogen as well as dietary protein and that the xanthine dehydrogenase response involves regulation of enzyme synthesis without changing the rate of degradation.