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Biomedical subjects

R J Solomon

Publications and source records attributed to R J Solomon.

At least 19 recordsLinked to original sources

Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.

Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus.

Acute Kidney Injury

Transport mechanisms that mediate the secretion of chloride by the rectal gland of Squalus acanthias.

The rectal gland of Squalus acanthias secretes chloride by a mechanism that has been termed "secondary active transport" because it depends on the activity of Na-K-ATPase. As currently described, chloride enters the cell across the basolateral cell membrane via the 2 chloride: sodium: potassium cotransporter. The energy for this electroneutral uphill movement of chloride and potassium is provided by the gradient for sodium directed into the cell. Present in the basolateral cell membrane is Na-K-ATPase that maintains the gradient for sodium. A potassium conductance, present as well in the basolateral cell membrane, recirculates the potassium. Chloride exits the cell across the luminal membrane via CFTR, the chloride conductance. This mechanism is widely distributed throughout vertebrates. This report reviews the experimental observations that led to the current definition of the mechanism of chloride transport in the rectal gland.

Animals

Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland.

The role of C-type natriuretic peptide (CNP) and its guanylyl cyclase-linked receptors in mediating salt secretion by the rectal gland of the spiny dogfish shark (Squalus acanthias) was investigated using HS-142-1, a competitive inhibitor of the binding of natriuretic peptides to their guanylyl cyclase receptors. CNP binds to receptors and activates guanylyl cyclase in rectal gland membranes in a way that is inhibited by HS-142-1. Guanylyl cyclase activation in rectal gland membranes is far more sensitive to CNP than to atrial natriuretic peptide, whereas the reverse is true for membranes derived from mammalian (rabbit) renal collecting duct cells. HS-142-1 inhibited the stimulatory effect of CNP on ouabain-inhibitable oxygen consumption by rectal gland tubules. In explanted rectal glands continuously perfused with blood from intact donor sharks, HS-142-1 inhibited the increase in salt secretion normally provoked by infusing isotonic saline solutions into the donor animal. These results strongly support the view that CNP released into the systemic circulation in response to volume expansion mediates the secretion of chloride by the rectal gland via receptors linked to guanylyl cyclase.

Adenylyl Cyclases

Fluoxetine in depressed patients on dialysis.

OBJECTIVE: To test the safety and efficacy of fluoxetine in patients with renal failure on dialysis. METHOD: Fourteen patients with major depression and end stage renal disease on hemodialysis were randomized into two groups for an eight-week study. Subjects as well as investigators were blinded as to which subject received fluoxetine and which placebo. Patients were carefully monitored concerning adverse events, serum fluoxetine and norfluoxetine levels, and psychological measurements of degree of depression. RESULTS: No patients discontinued treatment because of adverse events, all of which were minor. All psychological tests showed improvement in depression at the four-week and eight-weeks point, although statistical significance could only be demonstrated at the fourth week of this study. All patients in the active group had serum plasma concentrations of fluoxetine and norfluoxetine less than 250 ng/ml at eight weeks, similar to levels in patients with normal renal function in a previous open label study. CONCLUSIONS: This study confirms the relative safety of fluoxetine in depressed patients in renal failure on hemodialysis. It also suggests that fluoxetine may be efficacious in depressed patients on dialysis.

Adult

Fluoxetine in depressed patients with renal failure and in depressed patients with normal kidney function.

Nine depressed patients with normal kidney function and seven depressed patients with renal failure undergoing hemodialysis were treated with open-label fluoxetine 20 mg/day in an 8-week study. The study was designed to evaluate the pharmacokinetics of fluoxetine during repeated administration and to acquire preliminary data regarding the effectiveness of this antidepressant in a population undergoing hemodialysis. Six patients in each group completed the study. Of these, five patients undergoing hemodialysis and five patients with normal renal function experienced moderate to marked improvement in their depression. Side effects were equal and minor in both groups, indicating that fluoxetine is safe in patients with renal impairment. The mean +/- standard deviation steady-state plasma concentrations of the sum of fluoxetine plus its metabolite norfluoxetine for patients completing 8 weeks (N = 6, both groups) were comparable for the patients undergoing hemodialysis (253 +/- 61 ng/ml) and those with normal kidney function (218 +/- 122 ng/ml; t = 1.5, df = 70, p > 0.13). These data suggest that the efficacy of fluoxetine in patients with renal failure undergoing hemodialysis is comparable to that in patients with normal kidney function. These data further suggest that renal failure and the process of hemodialysis do not materially alter the pharmacokinetics of fluoxetine or its major metabolite norfluoxetine.

Adult

The rectal gland of Squalus acanthias: a model for the transport of chloride.

The rectal gland of the spiny dogfish shark, Squalus acanthias, secretes chloride by a furosemide sensitive process that has been termed "secondary active." Chloride enters the cell across the basolateral cell membrane via the sodium:potassium:2 chloride cotransporter. The energy for this electroneutral uptake step is provided by the electrochemical gradient for sodium directed into the cell. This is maintained by Na-K-ATPase present in the basolateral cell membrane. Present as well in the basolateral cell membrane is a potassium conductance that permits potassium to exit passively. Chloride leaves the cell across the luminal membrane via a chloride conductance closely similar to CFTR. The rectal gland is thus a model for the mechanism of secondary active chloride transport utilized by various epithelial organs throughout the vertebrate kingdom. This report reviews the humoral agents that regulate the secretion of chloride by the rectal gland and the intracellular mechanisms that mediate it. CNP, released from the heart in response to a volume stimulus, causes the release of VIP from nerves within the gland and together with VIP directly activates the rectal gland cell.

Animals

Legal considerations of medical-practice employee selection.

This article reviews the legal requirements that physicians face as employers, including Title VII of the Civil Rights Act of 1964, the Americans With Disabilities Act of 1990, and the Age Discrimination in Employment Act of 1967, as well as the preservation of at-will rights. It also describes the various employment methods that medical practices can use, including structured interviews, tests, work samples, simulations, references, drug tests, and application forms. Finally, the physician's role as supervisor of the employment process is discussed.

Age Factors

Interviewing prepubertal children about suicidal ideation and behavior.

OBJECTIVE: Much of the literature on assessment of suicidal children has focused on identifying risk factors associated with suicidal ideation and behavior in this population. Unique problems encountered in interviewing prepubertal children about suicidal ideation and behavior are examined in this paper. METHOD: Observations of problems encountered in interviewing prepubertal children about suicidal ideation and behavior were gleaned in the context of interviews of children admitted to a child psychiatry inpatient unit and interviews of the parents of these children. RESULTS: Unique problems include difficulties in assessment of suicidal intent, impact of cognitive development, particularly of the concept of death, interaction between current emotional state and memory of previous suicidal episodes, characteristics of play associated with suicidal states, effects of parents' attitudes toward assessment on information gathering, and the impact of certain risk factors on cognition and behavior during the interview. CONCLUSION: Interviewing children about suicidal ideation and behavior necessitates that the clinician attend to multiple elements of the interview simultaneously. These interviews are further complicated by the stressful thoughts and feelings that can be raised in both clinician and child in reaction to exploring the child's suicidal ideation and behavior. Additional research is needed to refine the process of reliable interviewing of children about suicidal ideation and behavior and to develop instruments both to quantitate the different elements of these interviews and to guide the clinicians conducting them.

Adolescent

The effect of mercury on chloride secretion in the shark (Squalus acanthias) rectal gland.

1. Mercuric chloride inhibited chloride secretion in a dose dependent way in isolated perfused rectal glands. The effect was readily apparent at a concentration of 10(-6) M and profound and irreversible at 10(-4) M. 2. The dithiol dithiothreitol (DTT) 10(-2) M completely prevented the effect of 10(-6) M mercuric chloride, reduced that at 10(-5) M and 10(-4) M, and made the inhibition at the latter concentration reversible. 3. Two organic mercurials, mersalyl and meralluride, that are effective diuretics in the mammalian kidney, and p-chloromercuribenzoyl sulfonic acid (PCMBS), that has no diuretic activity, had no effect on chloride secretion by the rectal gland. 4. The effect of mersalyl was not modified by lowering the pH of the solution perfusing the glands. 5. These results indicate that inorganic mercury and organic mercurials do not share the same mechanism of action. 6. The absence of an effect of organic mercurials on chloride transport in the rectal gland suggests that its effect on another chloride transporting epithelia, the thick ascending limb of the loop of Henle, is not mediated by inhibition of the chloride cotransporter or Na+, K(+)-ATPase, common to both epithelia.

4-Chloromercuribenzenesulfonate

Development of a radioimmunoassay to bradykinin using monoclonal antibodies.

We report here our success in the preparation of monoclonal antibody directed against bradykinin. We further demonstrate that the preparation is easier and less time-consuming compared to the preparation of polyclonal antibodies. The polyclonal antibody provides a ready source of the reagent very much required in the performance of the kinin radioimmunoassay. Limitation of this reagent was in the fact that it did not attain the desired specificity to distinguish between the kinin peptides. Nevertheless, it is interesting to note that the domains of recognition sites can be very similar for monoclonal or polyclonal response, particularly when the antigen is smaller (molecular size of about 1 Kd) as is the case with bradykinin. Our laboratory produced the first monoclonal antibodies at Brown University. These antibodies were directed to bradykinin in BALB-C mice and could recognize bradykinin, lysyl-bradykinin and met-lysyl-bradykinin. Using this reagent it is possible to develop and validate an RIA which can be utilized to measure total kinins in tissues and body fluids. Although this antibody shows similar specificity as found with the polyclonal antibody, the ease and shorter duration of this preparation may make it a reagent of choice.

Animals

Using a patient survey for marketing a professional health care practice.

Small, private, professional health care practices are at a disadvantage when conducting market survey research because they cannot afford to employ or purchase the expensive specialized marketing skills of their larger competitors. The author describes a method that small private practices can use to conduct patient marketing surveys. Survey findings are reported and examples are provided of how the results influenced subsequent marketing decisions. Suggestions are offered to help ensure the success of similar studies in other practices.

Analysis of Variance

Physician assistants as administrators. Opportunities in management. Panel discussion.

Physician assistants' involvement in administration focused on educational programs early in the profession's history. Recently, PAs have begun to work as administrators in hospitals and other settings. Preparation for management positions varies from on-the-job training to graduate degrees in business administration and public health. Clinical experience as a PA increases marketability in health care administration. Physician assistants who work as clinicians and administrators may find it difficult to balance responsibilities. In this forum, four PAs who helped pioneer this role explain how they became administrators and answer questions raised by other PAs interested in this growing job opportunity.

Health Facility Administrators

Effects of changing salt and water balance on renal kallikrein, kininogen and kinin.

The kallikrein-kininogen-kinin system (KKK) has been implicated in the renal sodium excretion response to changes in dietary sodium. However, both increases and decreases in the activity of this system have been observed when urinary sodium excretion is augmented by a variety of maneuvers. To further evaluate the potential physiologic role of this system, we measured three components of the KKK system in urine. Total kallikrein, intact kininogen, and kinin were measured twice in normal individuals during balance on both a high (250 mEq/day) or low (10 mEq/day) sodium intake. A consistent and significant reduction in the activity of all three components of the KKK system was noted during the high salt intake. Furthermore, during the high sodium intake, further acute reductions in components of this system were observed when an acute saline but not water load was administered. The consistent response of the various components of the KKK system to both acute and chronic sodium loading suggests that the system is physiologically linked to the regulation of sodium balance. However, the directional changes argue against a primary natriuretic effect of this system.

Aldosterone

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP.

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. These include: perfusion with procaine (10(-2) M), perfusion with high Mg2+ (9.5 mM) and low Ca2+ (0.5 mM) concentrations, and addition to the perfusate of the calcium channel blockers nifedipine (10(-6)M), diltiazem (5 X 10(-5)M), or verapamil (10(-4)M). Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal gland nerves, into the venous effluent or perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhance local release of neurotransmitters.

Adenosine

Comparative effects of pinacidil and prazosin on blood pressure, weight, plasma volume, the renin-angiotensin-aldosterone system, and the renal kallikrein-kinin system in patients with essential hypertension.

Patients with essential hypertension were randomized to treatment with either prazosin or pinacidil, a new direct-acting vasodilator. Factors that might modulate the antihypertensive response and result in pseudotolerance to these drugs were measured before initiation of therapy and following 12 weeks of treatment. Despite significant reductions in blood pressure, pinacidil and prazosin did not produce an increase in plasma volume, did not activate the renin-angiotensin-aldosterone system, and did not interfere with the renal kallikrein-kinin system. The data fail to reveal evidence of physiologic compensatory changes that would lead to the development of pseudotolerance.

Adolescent

Urinary kininogen: a possible regulator of kinin formation in normal individuals and subjects with essential hypertension, end-stage renal and liver disease.

Most previous studies have not significantly correlated urinary kallikrein to urinary kinins. We investigated whether urinary kininogen might influence kinin formation within the urine. On an ad-lib diet the 24 hour excretion of total and intact kininogen, kinins and kallikrein was determined in 24 control subjects, 20 untreated essential hypertensives, 12 with end-stage renal disease and 8 subjects with liver disease. Kallikrein and kinins were measured by a direct radioimmunoassay. Total kininogen was determined from the sum of preformed kinins and kinins generated after trypsin (intact kininogen). Cross reactivity between purified human low molecular weight kininogen and bradykinin antiserum was 3%. Total and intact kininogen were significantly correlated with kinins in controls, essential hypertension and liver disease. In essential hypertension, end-stage renal and liver diseases kinins were significantly decreased. This was associated with a reduction in kininogen but not kallikrein in essential hypertension and liver disease, and a reduction in kallikrein but not kininogen in end-stage renal disease. Thus, renal kinin generation in various states may be affected by either or both kininogen and kallikrein.

Humans