PubMed Health⌕ Search

Biomedical subjects

R Jeffs

Publications and source records attributed to R Jeffs.

8 recordsLinked to original sources
PubMed1999

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Adult↗
PubMed1999

Psychosexual dysfunction in males with genital anomalies: late adolescence, Tanner stages IV to VI.

OBJECTIVE: To assess psychosexual function in adolescent males with genital anomalies. METHOD: Fourteen consecutive males with bladder exstrophy-epispadias, 14 to 19 years old, Tanner stages IV to VI, were assessed along with their parents, using a developmental questionnaire, Hollingshead socioeconomic status rating, Child Behavior Checklist, Youth Self-Report, semistructured psychiatric interview, detailed sexual history, and 5 written, open-ended questions. RESULTS: All subjects showed psychosexual dysfunction in terms of genital satisfaction and genital touching; only 2 had ever undressed in front of anyone; only 2 had ever masturbated and only after age 16; 8 had few friends and only 5 considered any girls as friends; all expressed heterosexuality but only 4 had dated, 1 at age 17 and 2 after age 18; only the two 19-year-olds had experienced sexual intercourse, at the age of 19. All had an anxiety disorder. Half had experienced a major depressive disorder. CONCLUSIONS: Psychosexual dysfunction and anxiety were universal and chronic in these males with genital anomalies, leading to social and sexual developmental impairment. Half had a mood disorder. Implications for adulthood as well as for children with other genital anomalies are unclear but deserve further study. Males with genital anomalies should be evaluated for psychosexual developmental impairment.

Adolescent↗
PubMed1992

Hormones increase oxygen uptake in periportal and pericentral regions of the liver lobule.

The effect of several hormones known to alter intracellular free Ca2+ on rates of O2 uptake in periportal and pericentral regions of the liver lobule was studied in the perfused liver. Regional O2 uptake was measured by stopping the flow and monitoring the decrease in O2 concentration. When perfusion was in the anterograde direction, basal rates of O2 uptake were two to three times higher in periportal than in pericentral regions, and phosphorylase alpha activity, which increases as a function of intracellular free Ca2+ levels, was higher in periportal regions. In contrast, when perfusion was in the retrograde direction, rates of O2 uptake were two to three times greater in pericentral regions. Infusion of epinephrine (0.1 microM) or angiotensin II (5 nM) increased the rate of O2 uptake nearly exclusively in downstream areas of the lobule where O2 tension was low. When perfusions were in the anterograde direction, epinephrine increased phosphorylase alpha activity significantly only in pericentral regions. Stimulation of O2 uptake by epinephrine was blocked by the alpha-adrenergic receptor blocker phentolamine (1 microM) but not by the beta-receptor blocker propranolol. Thus hormones that increase intracellular calcium stimulate O2 uptake predominantly in regions of the liver lobule where O2 tension is lowest, supporting the hypothesis that oxygen tension regulates O2 uptake in the liver via mechanisms involving intracellular free Ca2+.

Adrenergic alpha-Antagonists↗
PubMed1988

Neonatal obstructive uropathy.

Neonatal obstructive uropathy is the leading cause of renal failure during infancy. A variety of upper and lower genito-urinary (GU) tract disorders may cause obstructive uropathy. The prompt diagnosis and evaluation of obstructive uropathy is imperative since appropriate intervention and follow-up can lead to excellent early recovery of function. The role of in utero diagnosis is primarily to alert physicians to the presence of obstructive uropathy and permit rapid initiation of care at birth or earlier in certain instances. The GU tract must be evaluated for evidence of dilatation, for reflux and for renal function using radionuclide studies, voiding cystourethrograms, cystoscopy and pyelography. The early course of neonatal obstructive uropathy has been improved by institution of GU diversion and primary repair, yet the effect of early surgical intervention and medical therapy in preventing renal failure remains unclear. Further studies are needed to identify prognostic features heralding progression to renal failure and how such progression can be prevented.

Female↗
PubMed1981

[Staged functional closure of bladder extrophy (author's transl)].

Two surgical alternatives exist in the treatment of classic bladder exstrophy: urinary diversion and functional closure. The staged ureterosigmoidostomy is the treatment of choice for patients not suitable for bladder and urethral reconstruction. The treatment of the patients selected for closure begins by closing the bladder during the neonatal period. Osteotomy appears to be necessary in children older than 2 days. Incontinence and vesico-ureteral reflux are treated by bladder neck-urethral reconstruction and reimplantation of the ureters at three years of age. Closure of the epispadias follows in the fifth year. It may be necessary to treat upper tract complications by secondary urinary diversion. Concerning incontinence, technical improvement in artificial sphincter may soon offer an alternative to urinary diversion. The results of 70 primary bladder closures selected from 94 patients presenting with bladder exstrophy are presented: 54 patients with long-term follow-up and completed staged repair were available for assessment: 31 (57.5%) proved to have a good result and 10 (18.5%) to have a fair results. 13 (24.0%) were completely incontinent or required diversion. Failures were thought to be the results of inadequate selection or failure to achieve continence.

Adolescent↗
PubMed1977

Ureterovesicoplasty: selection of patients, incidence and avoidance of complications. A review of 3,527 cases.

The procedure of ureteral reimplantation has certainly come of age. The incidence of complications can be kept low by careful selection of patients for operation along clear and definite guide lines, by close attention to detail in the surgical procedures and by rigorous followup care. When surgical intervention is deemed advisable the expected cure rate should be more than 94%. While complications do occur resultant damage to the upper urinary tracts should be minimized by its prompt recognition and by institution of appropriate therapy.

California↗