Biomedical subjects

R P Allen

Publications and source records attributed to R P Allen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Is excessive daytime sleepiness characteristic of Prader-Willi syndrome? The effects of weight change.

OBJECTIVES: To assess nighttime and daytime sleep patterns in patients with Prader-Willi syndrome and to examine the effects of weight change on excessive daytime sleepiness in patients with this disorder. DESIGN: Case series (within-subject design). SETTING: A university sleep disorders center. PATIENTS: Eight patients (5 males and 3 females), ranging in age from 5.5 to 21 years, who met the diagnostic criteria for Prader-Willi syndrome. INTERVENTIONS: Overnight sleep polysomnographic recording and daytime Multiple Sleep Latency Test. Four of the 8 patients were restudied after their weight had changed. MAIN OUTCOME MEASURES: Changes in the sleep disordered breathing rate and Multiple Sleep Latency Test measures. RESULTS: Sleep-disordered breathing occurred in all patients and was principally characterized by obstructive hypoventilation or episodes of apnea that occurred primarily during rapid eye movement sleep. After weight reduction, 3 patients had respiratory values that were within the broad normal range (disordered breathing rate, < 15 breaths per hour). Statistically significant (P < .05) weight loss effects occurred during nonrapid eye movement sleep (decrease with weight loss, F = 6.243). Excessive daytime sleepiness was documented in 6 of 7 patients who completed the Multiple Sleep Latency Test. Excessive daytime sleepiness was not consistently correlated with body weight or any of the nocturnal sleep variables. CONCLUSIONS: A sleep-related breathing disorder occurred during rapid eye movement and nonrapid eye movement sleep and improved with weight change in patients with Prader-Willi syndrome, emphasizing the importance of weight reduction in clinical management. However, excessive daytime sleepiness persisted despite a reduction in sleep-disordered breathing after weight loss, suggesting a primary disturbance of sleep. Our findings provide additional support for the view that primary hypersomnia is a characteristic feature of the Prader-Willi syndrome.

Adolescent↗

PubMed1996

Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients.

Carbidopa/levodopa has become accepted as a primary treatment for both the restless legs (RL) syndrome and periodic leg movements in sleep (PLMS). It, however, usually significantly augments the RL symptoms in the day as well as night, requiring medication change for about 70% of the patients. The dopaminergic agonist pergolide provides a potentially useful treatment; doses given at dinner and before bed could suffice to treat the symptoms for most of the 24-hour day. A series of consecutive patients with RL syndrome or PLMS was studied using a standard medication protocol starting with carbidopa/levodopa, switching if needed to pergolide and, finally, to an opiate or other treatment. For 51 patients entered into the study, 21 (39%) continued on carbidopa/levodopa and 26 (50%) switched to pergolide. For those tried on pergolide, 19 (73%) responded well. Restless legs augmentation occurred for only four (15%) and was severe enough to require medication change for only one (4%) of these patients. The patients with PLMS responded best to carbidopa/levodopa, whereas severe RL patients responded best to pergolide. Pergolide provided a good treatment for the RL syndrome, particularly for the more severe RL cases without significant problems with RL augmentation.

Antiparkinson Agents↗

PubMed1996

Augmentation of the restless legs syndrome with carbidopa/levodopa.

Dopaminergic agents and carbidopa/levodopa have become the preferred treatment for both the restless legs (RL) syndrome and for periodic limb movements in sleep (PLMS). For once-nightly treatments with carbidopa/ levodopa, a problem with morning end-of-dose rebound increases in leg movements has been reported to occur in the about one-fourth of the patients. In our clinical studies a previously unreported but far more significant problem of markedly augmented RL symptoms occurred in the afternoon and the evening prior to taking the next nightly dose. A systematic prospective evaluation of this augmentation in 46 consecutive patients treated with carbidopa/ levodopa for RL syndrome or PLMS disorder found this augmentation to be the major adverse effect of treatment. Augmentation occurred for 31% of PLMS patients and 82% of all RL patients. It was greater for subjects with more severe RL symptoms and for patients on higher doses (> or = 50/200 mg carbidopa/levodopa) but was unrelated to gender, age or baseline severity of PLMS. This augmentation was severe enough to require medication change for 50% of the RL patients and 13% of PLMS patients. Augmentation resolved with cessation of the medication and could be minimized by keeping the dose low.

Carbidopa↗

PubMed1996

Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system.

PURPOSE: The effects of androgen replacement via a nonscrotal permeation enhanced testosterone transdermal system on the sexual function of men with hypogonadism were assessed. MATERIALS AND METHODS: An open label, multicenter study of testosterone supplementation and withdrawal was conducted with sexual function assessed by the Watts and Davidson questionnaires and RigiScan monitoring. RESULTS: When comparing results obtained during use of the testosterone transdermal system (with normalized testosterone levels) and during the androgen withdrawal period, nocturnal erections occurred more frequently with longer duration and greater rigidity, and patient assessments of sexual desire and weekly number of erections were higher. CONCLUSIONS: Sexual function improved significantly in men with hypogonadism treated with the testosterone transdermal system.

Administration, Cutaneous↗

PubMed1995

Evaluation of erectile function in men with sickle cell disease.

OBJECTIVES: To evaluate and characterize erectile manifestations associated with sickle cell disease using nocturnal penile tumescence testing with polysomnography (NPT/PSG) and magnetic resonance imaging (MRI) of the penis. METHODS: Six variably potent men with sickle cell disease, of whom 5 reported a history of priapism, underwent comprehensive evaluations of erectile function. Evaluations involved a medical history and physical examination with completion of priapism and sexual function questionnaires, followed by NPT/PSG and MRI of the penis. RESULTS: Many different erectile abnormalities were identified in this group using NPT/PSG, although nocturnal erection durations as well as detumescence times were uniformly prolonged. Various axial rigidity measurements were obtained, which correlated fairly well with individual reports of erectile function. MRI findings ranged from normal corporeal anatomy to corporeal destruction with intracorporeal fibrosis and hemosiderin deposition. CONCLUSIONS: In sickle cell disease, the erectile dysfunction that commonly occurs may be markedly different among men with this disease and may not always be predicted on the basis of clinical history of priapism. Generally, clinical assessments of erectile function may be derived from clinical histories and physical examinations. NPT/PSG and MRI of the penis are in accord with these assessments, obviating their routine use, although they may be valuable management adjuncts in certain situations.

Adolescent↗

PubMed1995

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Deoxyribonuclease I↗

PubMed1994

Comparison of duplex ultrasonography and nocturnal penile tumescence in evaluation of impotence.

Duplex ultrasound is used commonly to evaluate vascular function in impotent men. There is evidence, however, that some men with normal vascular function may have falsely abnormal duplex ultrasound results because of suppression of response to pharmacological stimulation due to anxiety. We performed a prospective blinded study of 40 impotent men comparing duplex ultrasound to a formal nocturnal penile tumescence evaluation. Duplex ultrasound was done with a standard 10 MHz. color Doppler unit after intracorporeal pharmacological stimulation. Nocturnal penile tumescence was performed at a sleep laboratory, and included measurements of penile circumference, axial rigidity, arterial pulsations, and direct patient and observer evaluation of erections. Of 40 men 20 had an abnormal duplex ultrasound result (maximum arterial velocity less than 30 cm. per second), including 9 who had normal nocturnal penile tumescence with at least 1 rigid erection (greater than 550 gm. axial rigidity) lasting at least 5 minutes. All 9 men had evidence of psychogenic dysfunction on history and personality inventory, and only 1 had evidence of vascular disease. Of the other 11 patients with abnormal duplex ultrasound and nocturnal penile tumescence findings, only 2 had evidence of psychogenic impotence and 9 had evidence of vascular disease. In these 11 men there were significant correlations between maximum arterial velocity on duplex ultrasound, and maximum rigidity and arterial pulsations on nocturnal penile tumescence. Of 40 patients 20 had a normal duplex ultrasound finding (maximum velocity greater than 30 cm. per second). Nine of these patients had a normal nocturnal penile tumescence test, of whom 5 had evidence of psychogenic impotence and only 1 had evidence of vascular disease. Eleven men with normal duplex ultrasound had an abnormal nocturnal penile tumescence test, including only 2 with any evidence of psychogenic impotence, while 9 had vascular disease and 1 had a history of neurological disease. Based on this study 9 of 14 men (64%) with a normal nocturnal penile tumescence test and other evidence of psychogenic impotence had abnormal duplex ultrasound. Therefore, an abnormal duplex ultrasound study should be interpreted cautiously if there is evidence of psychogenic impotence. In men with vasculogenic impotence there is an excellent correlation and cross-validation between maximum velocity on duplex ultrasound, and axial rigidity and arterial pulsations on nocturnal penile tumescence.

Adult↗

PubMed1994

Controlled drinking and abstinence in alcoholic men: beliefs influence actions.

A group of alcoholic men were asked 8 years postdischarge from hospital if they could drink alcohol with control. Subjects who said "no" (the NCD group) were compared to those who said "yes" (the CD group). A majority of the NCD group had been abstinent during the year preceding the 8-year evaluation, whereas none of the CD group had been. In the model developed, troubles resulting from drinking are seen as instrumental in changes from a CD to a NCD belief. The clinical relevance of our results is discussed.

Adult↗

PubMed1993

Comparison of RigiScan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity.

Evaluation of male erectile function ideally should include measurement of axial rigidity expressed as grams force required to produce penile buckling. An axial rigidity more than 550 gm. is generally considered adequate for vaginal penetration. Unfortunately, this test cannot be done frequently and may disrupt sleep. An alternative method of determining rigidity is to use the RigiScan,* which makes repetitive measurements of radial rigidity at the base and tip of the penis expressed as per cent of normal maximum. Previous studies have demonstrated a positive correlation between axial and radial rigidity measurements but they have not been compared in patients with a wide range of erectile function. We performed a prospective study in a consecutive series of patients presenting with impotence comparing axial rigidity measured with a tonometer and radial rigidity measured by RigiScan. Erectile rigidity also was evaluated by a trained, blinded observer. Overall, RigiScan base and tip radial rigidity correlated well with axial rigidity (p < 0.002) and observer ratings (p < 0.003); axial rigidity similarly correlated well with observer ratings (p < 0.0001). However, when RigiScan base and tip radial rigidity exceeded 60% of maximum, there was a poor correlation with axial rigidity and observer ratings (p > 0.1). In this range, the RigiScan failed to discriminate axial rigidities between 450 and 900 gm. buckling force; however, axial rigidity in this same range again correlated well with observer ratings (p < 0.0001). Since an axial rigidity of more than 550 gm. is considered adequate for vaginal penetration, the RigiScan may not be able to detect mild abnormalities in erectile function. Further study is in progress to evaluate the significance of these findings but presently a RigiScan measurement of radial rigidity in excess of 60% of maximum should be interpreted cautiously and not necessarily regarded as normal. In this range further measurements of axial rigidity or observer ratings of rigidity may be necessary to establish the diagnosis.

Erectile Dysfunction↗

PubMed1993

Persistent effects of (+/- )3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on human sleep.

(+/- )3,4-methylenedioxymethamphetamine (MDMA) is a recreational drug of abuse which damages serotonin neurons in animals. It is not known whether MDMA is also neurotoxic in humans, and if so, whether there are functional consequences. Given the putative role of serotonin in sleep, it was hypothesized that one manifestation of serotonin neurotoxicity in humans might be disturbances of sleep. To determine whether MDMA use has effects on sleep, all-night polysomnograms of 23 MDMA users were compared to those of 22 age- and sex-matched controls. On average, MDMA users had 19 minutes less total sleep and 23.2 minutes less non-REM (NREM) sleep than controls. These statistically significant differences in NREM sleep were due primarily to an average of 37 minutes less stage 2 sleep, with no significant differences noted in stages 1, 3 or 4. Although it is not known whether the alterations in sleep observed in MDMA users are due to serotonin neurotoxicity, the present findings suggest that MDMA use can lead to persistent changes in CNS structures involved in human sleep generation.

3,4-Methylenedioxyamphetamine↗

PubMed1993

A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene.

We studied the relative benefits of carbidopa/levodopa (25/100 mg and 50/200 mg) and propoxyphene (100 mg and 200 mg) in six subjects with periodic limb movements (PLM) using a randomized, double-blind, placebo-controlled, cross-over design with a 4-day placebo wash-out period between test medications. Each subject received, for successive 2-week periods, 4 days of placebo followed by 5 days of low-dose and then 5 days of high-dose medication. Outcome was measured with polysomnograms and sleep latency tests on the last night of the high dose, and leg activity was monitored for each night of the study. Carbidopa/levodopa normalized PLM and improved sleep, particularly in the first 3 hours in most subjects. Propoxyphene had marginal benefit and significantly decreased arousals and mildly decreased leg movements for leg activity monitoring, but not for PLM on the polysomnograms. Subjects reported better sleep and alertness on carbidopa/levodopa than on propoxyphene or placebo. Our results support the premise of a central dopaminergic abnormality in PLM.

Adult↗

PubMed1993

Survival of patients undergoing Nd:YAG laser therapy compared with Nd:YAG laser therapy and brachytherapy for malignant airway disease.

Brachytherapy in combination with Nd:YAG laser therapy may add to the duration of survival of the palliative period when compared with laser alone. A retrospective study of patients with inoperable squamous cell carcinoma (SCC) was undertaken to determine if there was a difference in survival between those patients treated with Nd:YAG laser alone and those treated with Nd:YAG laser and brachytherapy. Twenty-two patients were treated with brachytherapy for malignant airway disease at our institution of which 13 had SCC. All patients had previously received treatment with Nd:YAG laser for exophytic disease. Survival was compared with those patients treated with Nd:YAG laser alone for SCC involving the airway. There was no statistical difference between the two groups with regard to age. The duration of survival of patients with SCC of the airway from the first Nd:YAG laser treatment was determined. A significant difference between those patients treated with Nd:YAG laser alone and those patients treated with combined therapy was found (p < 0.001). Brachytherapy may potentiate the duration of survival in patients with SCC involving the airway compared to palliation with Nd:YAG laser alone.

Aged↗

PubMed1992

Beta-blocker effects on 24-h activity in normotensive and renovascular hypertensive baboons.

Spontaneous motor activity of normotensive and renovascular hypertensive baboons was measured during oral dosing with the beta-adrenergic antagonists atenolol HCl (2.6 mg/kg/day) and d,l-propranolol HCl (6.8 mg/kg twice daily) in separate studies. Each study administered active drug for 21 consecutive days. Piezoelectric monitors sensitive to movement were worn continuously by the baboons. Propranolol decreased overall 24-h average activity during the third week of dosing in normotensive baboons but not in renovascular hypertensive baboons. The greatest reductions in activity averaged 20% at those times of day corresponding to the second daily drug dose both in normotensive baboons and, at this time of day only, in the majority of hypertensive baboons. Activity decreases reversed to baseline levels when propranolol was discontinued. For atenolol, most normotensive but no hypertensive baboons showed decreases in activity at the time of day corresponding to the daily drug dose.

Adrenergic beta-Antagonists↗

PubMed1992

General activity in baboons measured with a computerized, lightweight piezoelectric motion sensor: effects of drugs.

A small, 1-oz activity-monitoring device is described for measuring motor activity continuously for periods of up to 42 days. The monitor employs a piezoelectric sensor that detects extremely small accelerations induced by movements. The monitor can be placed on collars or harnesses (e.g., for rabbits, cats, dogs, nonhuman primates, etc.). The use of the monitor is described within numerous laboratories studying the behavioral pharmacology of drugs in individually caged laboratory baboons. Patterns of daily activity were reliably recorded over periods of several months, and reflected the normal activity patterns of animals. The activity monitor recorded reliable, drug-induced changes in general activity that paralleled the known effects of the same drugs on learned behaviors. Low doses of the stimulants cocaine and d-amphetamine both increased general activity. Marked reductions in general activity were observed following both the administration of delta-9-tetrahydrocannabinol and an antihypertensive drug combination of diuretic and verapamil.

Animals↗

PubMed1992

Chronic hydrochlorothiazide and verapamil effects on motor activity in hypertensive baboons.

Spontaneous motor activity was measured in six baboons during chronic oral dosing with a diuretic (hydrochlorothiazide/triamterene), a calcium channel blocker (verapamil), and a combination of the two drugs. Piezoelectric monitors sensitive to movement were attached to leather collars and were worn continuously by the baboons throughout the protocol. Baboons were made hypertensive during a preexperimental period by either 1) chronic administration of deoxycorticosterone acetate (DOCA)-salt or 2) surgical renal artery stenosis. Total inactive periods/day increased over baseline levels during diuretic alone and increased further during diuretic + verapamil combined. The total number of inactive periods/day returned toward baseline levels in the subsequent conditions of verapamil alone and baseline recovery. Activity levels decreased during combination dosing mainly during morning hours (0700-1100 h). Overall changes in activity occurred in the second week of dosing; this time period was found earlier to maximally decrease blood pressure and to impair behavioral performances.

Animals↗

PubMed1992

Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1.

We performed a double-blind, crossover study using objective measurements to compare maximum rigidity and duration of erections with papaverine hydrochloride in combination with phentolamine mesylate and/or prostaglandin E1. The rationale for the protocol was to combine a smooth muscle relaxant (papaverine) with either or both vasodilating agents (phentolamine and prostaglandin E1) commonly used for injection therapy. The 7 volunteer patients with organic impotence documented by abnormal nocturnal penile tumescence testing were injected with 0.5 to 1.0 ml. papaverine (30 mg./ml.) in combination with phentolamine (0.5 mg./ml.) and/or prostaglandin E1 (5 micrograms./ml.). Each patient received 2 injections on each of 2 testing dates; injection 2 was given after tumescence resulting from injection 1 had subsided completely. The medications were given in a randomized, counterbalanced order following double-blind procedures. Patients evaluated the erections subjectively. In addition, the RigiScan device was used to measure maximum rigidity and duration of erections. All patients observed increased duration of erections with both combinations containing prostaglandin E1. Analysis of RigiScan measurements showed no statistically significant differences for maximum rigidity (p greater than 0.1) but significantly greater duration of erections with papaverine plus prostaglandin E1, and papaverine plus phentolamine plus prostaglandin E1 compared to papaverine plus phentolamine (p less than 0.001). There was no statistical difference in rigidity or duration of erections between papaverine plus prostaglandin E1 and papaverine plus phentolamine plus prostaglandin E1. No patient reported significant penile pain with any of the injections. We conclude that the combination of papaverine and prostaglandin E1 produces erections of longer duration than papaverine plus phentolamine and that no additional benefit is gained by adding phentolamine to a combination of papaverine and prostaglandin E1. Further studies are in progress to define optimal dose response curves for papaverine and prostaglandin E1 as individual agents and in combination.

Alprostadil↗

PubMed1991

Steroids and biologic agents in the intensive care unit.

We have reviewed the actions, indications, and toxicity of steroids and several important biologic pharmaceutical agents used in critical care medicine. This is a rapidly expanding area of therapeutics. Space limitations prevent an exhaustive review of all biologic pharmaceuticals, such as tissue plasminogen activating substance, hormones (e.g., thyroid, insulin, growth hormone, erythropoietin), clotting factors, and blood products. The future of biologic pharmaceuticals appears to be bright in the face of new biotechnology, and the critical care physician can anticipate new and exciting treatments to evolve from current basic and clinical research into biologic agents.

Critical Care↗

PubMed1990

Nd:YAG laser bronchoscopy. Rigid or fiberoptic mode?

One hundred twenty four Nd:YAG laser procedures were performed on 79 patients (age range, 25 to 89 years) over a five-year period at our institution. Over 90 percent of patients had malignant tumors. The fiberoptic bronchoscope (FOB group) was used exclusively during the first two years (61 cases, 32 patients). All except four of these cases utilized conscious sedation and local anesthesia. Subsequent to this, the rigid bronchoscope (RB group) was used as the primary instrument under general anesthesia (51 cases, 42 patients). Twelve cases combined both bronchoscopic modalities (combined group, 12 patients). The percentage improvement in proximal airway lumen diameter post-Nd:YAG laser therapy was significantly greater using the RB (p less than 0.05). For distal lesions, the FOB was superior (p less than 0.05). There was no difference in the complication or survival rates between the groups. Our data suggest that whenever possible, the RB should be used to treat proximal lesions, and the FOB should be used for distal lesions. Both bronchoscopes are often used together. Hence, laser bronchoscopists should be proficient in both bronchoscopic techniques.

Adult↗