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Biomedical subjects

R P Goodman

Publications and source records attributed to R P Goodman.

At least 19 recordsLinked to original sources
PubMed2005

Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication.

Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on a side, that can self-assemble in seconds with near-quantitative yield of one diastereomer. They can be connected by programmable DNA linkers. Their triangulated architecture confers structural stability; by compressing a DNA tetrahedron with an atomic force microscope, we have measured the axial compressibility of DNA and observed the buckling of the double helix under high loads.

Base Pairing↗
PubMed2005

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗
PubMed1999

Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients.

BACKGROUND: Staphylococcus aureus is a common cause of serious infection in patients infected with HIV. OBJECTIVES: To evaluate risk factors for and quantitative effect of S. aureus infection in HIV-infected patients, with special attention to nasal carriage. DESIGN: Prospective, multihospital cohort study. SETTING: Three tertiary care Veterans Affairs Medical Centers. PARTICIPANTS: 231 ambulatory HIV-infected patients. RESULTS: Thirty-four percent of patients were nasal carriers of S. aureus. Of these patients, 38% were persistent carriers and 62% were intermittent carriers. Twenty-one episodes of infection occurred in 13 patients: Ten were bacteremias (including 2 cases of endocarditis), 1 was pneumonia, and 10 were cutaneous or subcutaneous infections. Seventeen (85%) of these episodes occurred in patients with CD4 counts less than 100 cells/mm3. Recurrent infections occurred in 3 of 7 patients who survived an initial S. aureus infection. The mortality rate was higher among patients with S. aureus infection than among those without infection (P = 0.03). Factors significantly associated with S. aureus infection were nasal carriage, presence of a vascular catheter, low CD4 count, and neutropenia. Molecular strain typing indicated that for 6 of 7 infected patients, the strain of S. aureus isolated from the infected sites was the same as that previously cultured from the nares. CONCLUSION: Nasal carriage is an important risk factor for S. aureus infection in HIV-infected patients. Controlled studies are indicated to determine whether eradication of nasal carriage in a selected subset of patients (for example, those with a low CD4 cell count) might prevent invasive S. aureus infection in patients with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1991

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study.

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.

Adult↗
PubMed1991

The effect of phenylpropanolamine on 24-hour blood pressure in normotensive subjects administered indomethacin.

We evaluated the effect of phenylpropanolamine hydrochloride (PPA) in 14 young, healthy, normotensive women who concurrently received indomethacin. Subjects received sustained-release (SR) indomethacin 75 mg bid and were randomly assigned to receive double-blind SR PPA 75 mg/d or placebo for four days. After a six-day washout period, subjects were crossed over to the opposite four-day double-blind treatment. Following an additional six-day washout period, subjects received indomethacin placebo and PPA placebo during a final, single-blind four-day period. Twenty-four-hour blood pressure (BP) monitoring every 30 minutes and a 24-hour urine collection for prostaglandin E2 (PGE2) were performed on the fourth day of each treatment period. Compliance with the medication regimen was confirmed by drug concentrations, pill counts, and urinary PGE2 concentrations. Compared with the indomethacin and placebo treatment periods, the combination of indomethacin and PPA had no significant effect on mean systolic or diastolic BP during the 24-hour study period or during any four-hour interval. We conclude that the combination of SR PPA 75 mg/d and SR indomethacin 150 mg/d for four days has no adverse effect on BP in normotensive women.

Adult↗
PubMed1991

Renin profile, race, and antihypertensive efficacy with atenolol and labetalol.

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.

Atenolol↗
PubMed1988

Isradipine (PN 200-110) versus hydrochlorothiazide in mild to moderate hypertension. A multicenter study.

The effects of 10 weeks of treatment with isradipine (ISRP), a new dihydropyridine Ca antagonist, was evaluated in a prospective, randomized, double-blind, parallel group, hydrochlorothiazide (HCTZ) controlled study in patients with mild to moderate hypertension. Of 98 patients enrolled, 73 completed the study and were deemed valid for efficacy analyses; 36 in the ISRP group and 37 in the HCTZ group. Monotherapy with ISRP significantly (P less than 0.001) decreased (mean +/- SD) sitting systolic blood pressure (BP) from 146 +/- 11 mm Hg to 128 +/- 11 mm Hg and diastolic BP from 100 +/- 4 mm Hg to 83 +/- 5 mm Hg. Heart rate during the plateau period was not significantly different (76 +/- 11 vs 78 +/- 11 bpm) between the ISRP and HCTZ groups. These reductions in BP were comparable to monotherapy with HCTZ. The mean reduction in diastolic BP with ISRP (17 +/- 6 mm Hg) was significantly (P less than 0.05) greater than that with HCTZ (14 +/- 5 mm Hg). The mean doses for ISRP and HCTZ were 12 mg/day and 60 mg/day, respectively. There was no significant difference in frequency of common side effects (headache, nausea, fatigue, dizziness, palpitations) between the two groups. However, transient or intermittent peripheral edema occurred more frequently in ISRP group. Four patients in ISRP group (two due to edema and two due to palpitations) and two patients in HCTZ group (due to poor BP control) were discontinued from the study. Our results indicate that ISRP in doses of 5 to 10 mg bid is as effective as HCTZ as monotherapy in the treatment of mild to moderate hypertension.

Blood Pressure↗
PubMed1987

Effect of high-dose ibuprofen on 24-hour blood pressure in healthy women.

The nonsteroidal antiinflammatory drug (NSAID) indomethacin has been shown to increase blood pressure in normotensive individuals. The effect of other NSAID on blood pressure has not been as well studied. We evaluated the effects of ibuprofen, an NSAID currently available without a prescription, on 24-hour ambulatory blood pressure in ten young, healthy, normotensive women. Using a randomized, crossover, double-blind design, subjects received ibuprofen 800 mg and a placebo identical in appearance to ibuprofen three times a day for eight days with a washout period between regimens. Subjects were instructed to follow a no-added salt diet during the study. Twenty-four-hour blood pressure monitoring and 24-hour urine collection for prostaglandin E2, creatinine, and sodium were performed on days 1 and 8 of each study week. Tablet counts and a 40 percent reduction in urinary prostaglandin E2 documented compliance with ibuprofen. Ibuprofen had no significant effect on systolic or diastolic blood pressure at any hour during the 24-hour period. Mean blood pressure for the 24-hour period was 112/73 and 111/73 mm Hg on day 1 and 111/73 and 112/73 mm Hg on day 8 for placebo and ibuprofen, respectively. We conclude that ibuprofen at doses as high as 2400 mg/d for up to seven days has no effect on blood pressure in normotensive women. Further studies are needed in hypertensive subjects.

Adult↗
PubMed1986

The effect of phenylpropanolamine on ambulatory blood pressure.

Phenylpropanolamine (PPA) is a sympathomimetic amine and component of many over-the-counter decongestants and anorectic agents. It has been reported to cause elevated blood pressure and even hypertensive crises. The pressor effects with therapeutic doses are not well established. We monitored the effects of acute and chronic PPA dosing using 24-hour ambulatory blood pressure recording as a sensitive method of monitoring blood pressure variability. Eighteen normotensive male subjects were randomly assigned to receive 75 mg PPA (sustained-release preparation) or placebo in a double-blind crossover design with blood pressure monitored on days 1 (D1) and 6 (D6) of each period. There was no significant difference in blood pressure when compared as either 2-hour intervals or 24-hour global means: (placebo) 116/68 (D1), 117/68 (D6); (PPA) 118/69 (D1), 119/69 (D6). Our results document the absence of pressor effect with PPA in therapeutic doses even with repeated measurements and further confirm the reproducibility of 24-hour blood pressure monitoring.

Adult↗
PubMed1986

Labetalol by continuous intravenous infusion in severe hypertension.

This study documents our experience with labetalol administered by continuous intravenous infusion for severe hypertension. Infusions were performed in 14 hospitalized patients (15 infusions) with supine diastolic pressure greater than 125 mmHg or supine systolic pressure greater than 200 mmHg. Blood pressures were measured by intra-arterial recording or an Arteriosonde 1225 Doppler instrument standardized with a mercury sphygmomanometer. Patients initially received 2 mg/min continuous infusion; the infusion rate varied between 0.5 and 2.0 mg/min according to the protocol. The infusion was terminated when diastolic pressure decreased 30 mmHg or when 300 mg of the drug had been infused. Goal blood pressure was achieved in all but two infusions. Sedation was the most common adverse reaction, followed by nausea and diaphoresis. No patient required discontinuation or reduction in infusion rate secondary to side effects. We conclude that continuous intravenous infusion of labetalol offers an effective alternative to current parenteral therapy.

Adult↗
PubMed1985

Inhibition of platelet aggregation and thromboxane production by pinacidil.

We examined the effects of pinacidil on in vitro platelet function and arachidonic acid metabolism. Pinacidil is an arterial vasodilator currently undergoing clinical trials. Although its mechanism of action is yet undetermined, there is evidence that the activity of other vasodilators may in part be mediated through their effects on arachidonic acid metabolism. Alterations in platelet function were investigated by measuring ADP-induced aggregation in aliquots of human platelet rich plasma that were preincubated with pinacidil. Changes in arachidonic acid metabolism were determined using washed platelets incubated with 14C labeled arachidonic acid after preincubation with pinacidil or indomethacin. The arachidonate metabolites formed were extracted, separated by thin layer chromatography and quantitated via liquid scintillation spectrometry. Pinacidil inhibited platelet aggregation in a concentration dependent manner with 94% inhibition at 0.005M pinacidil. Pinacidil also caused concentration dependent inhibition of TXB2 production (63% inhibition at 0.01M) with reciprocal increases in PGE2 and PGF2 alpha production. There was no significant alteration in arachidonic acid utilization. Indomethacin (0.01M), as expected, inhibited TXB2 as well as PGE2 and PGF2 alpha synthesis. We conclude that, under the conditions of our assay, pinacidil inhibits platelet aggregation and specifically inhibits thromboxane synthetase, an action different from that of indomethacin. Alterations in the relative synthesis of vasodilating and vasoconstricting prostaglandins may be one mechanism whereby pinacidil exerts its antihypertensive activity.

Arachidonic Acid↗
PubMed1984

Endogenous prostacyclin synthesis is decreased during activation of the renin-angiotensin system in man.

Prostacyclin has been implicated as a mediator of renin release, whereas angiotensin II evokes prostaglandin I2 (PGI2) release from both vascular and nonvascular tissues in vitro. The physiological significance of these observations was assessed by measurement of an index of endogenous prostacyclin biosynthesis in human volunteers during varied activation of the renin-angiotensin system secondary to manipulation of dietary sodium. Excretion of the major urinary metabolite of prostacyclin in man, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), fell from 295 +/- 51 to 176 +/- 35 (+/- SEM) ng g creatinine-1 (P less than 0.01) in 10 normal subjects when sodium intake was decreased from 150 to 10 meq/day. In five patients with primary hyperaldosteronism, PGI-M fell from 199 +/- 34 ng g creatinine-1 preoperatively to 120 +/- 26 pg/mg creatinine-1 after removal of the adenoma. In such patients, the reduction in PGI-M was associated with a significant increase in PRA. Thus, in both normal subjects and patients with hyperaldosteronism, PGI-M excretion fell rather than increased with activation of the renin-angiotensin system. This suggests that systemic biosynthesis of PGI2 is unrelated to renin release and that angiotensin II is unlikely to stimulate endogenous prostacyclin biosynthesis under these conditions in man.

Adenoma↗
PubMed1982

Prostacyclin production during pregnancy: comparison of production during normal pregnancy and pregnancy complicated by hypertension.

We investigated prostacyclin (PGI2) biosynthesis during pregnancy by measuring urinary excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (dinor) and 15-keto-13,14-dihydro-2,3-dinor-6-keto-prostaglandin F1 alpha (15 kd dinor) with the use of specific gas chromatography-mass spectrometry assays. Nine normotensive nonpregnant women, five normotensive women in the mid-trimester of pregnancy, eight normotensive women in the third trimester of pregnancy, and six women who developed hypertension during the third trimester provided 24-hour samples of urine. Normal pregnant women had a fivefold increase in urinary excretion of dinor in comparison to nonpregnant women (253 +/- 21 ng dinor/gm creatinine for controls vs. 1,224 +/- 110 and 1,127 +/- 152 for second and third trimesters) (mean +/- SEM). Pregnant subjects with hypertension had a significant (50%) reduction in urinary dinor excretion in comparison to normotensive pregnant subjects (561 +/- 105 ng dinor/gm creatinine). In subjects selected from each group, the ratio of dinor to 15 kd dinor remained constant. We conclude that PGI2 biosynthesis is increased during normal pregnancy, and that this increase is less in pregnancy-induced hypertension. This raises the possibility that PGI2 helps mediate hemodynamic changes during normal pregnancy, and that a relative decrease in production might be related to the pathogenesis of pregnancy-induced hypertension.

Adult↗