Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study

OBJECTIVE: To evaluate the decrease in nocturnal polyuria and the tolerability of three different doses of oral desmopressin in elderly subjects. SUBJECTS AND METHODS: Subjects were included in the study if they; (i) were healthy and free from medication with possible influence on their diuresis or voiding pattern: (ii) had an increased nocturnal frequency (> or = 2 nocturnal voids, as reported in the pre-screening period); and (iii) had a nocturnal urinary output of > or = 0.9 mL/min. Seventeen men and six women (mean age 68.1, SD 4.7 years) met these criteria and were treated with 0.1, 0.2 and 0.4 mg oral desmopressin given at bedtime, each dose taken for one week on three consecutive weeks. RESULTS: The mean (SD) nocturnal diuresis before treatment was 1.6 (0.7) mL/min, which decreased significantly to 1.1 (0.4) mL/min when 0.1 mg desmopressin was given. A dose of 0.2 mg desmopressin resulted in a further small decrease in the nocturnal diuresis to 0.9 (0.4) mL/min, whereas the 0.4 mg dose produced no additional effect. The reduction in nocturnal diuresis occurred almost exclusively in the group with a nocturnal urinary output of > or =1.3 mL/min. After treatment, diuresis returned to pretreatment levels. There was no change in body weight or in ankle circumference during desmopressin treatment and no serious adverse effects were observed. CONCLUSION: Desmopressin reduces nocturnal diuresis in polyuric elderly subjects and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose-dependent way.     

Nocturnal polyuria and natriuresis in male patients with nocturia and lower urinary tract symptoms

PURPOSE: We investigated the circadian variation in urine output, plasma angiotensin II, aldosterone, atrial natriuretic peptide, arginine vasopressin and blood pressure. MATERIALS AND METHODS: We studied 17 elderly men with nocturia and lower urinary tract symptoms, and 10 age matched controls without nocturia. RESULTS: Of the 17 patients studied 11 had a lack of diurnal variation in urine output and increased nocturnal urine production associated with increased nocturnal sodium excretion, and 6 had a diurnal variation in urine output comparable to controls. CONCLUSIONS: Nocturia in a large proportion of elderly men with lower urinary tract symptoms is caused by nocturnal polyuria and natriuresis.     

Desmopressin in the management of nocturia in patients with multiple sclerosis. A double-blind, crossover trial

BACKGROUND: Neurogenic bladder affects up to 80% of patients with multiple sclerosis (MS) and, in 50% of these patients, it is a significant cause of disability. The current management of neurogenic bladder, based on fluid restriction, anticholinergic agents, intermittent self-catheterization, and, in some cases, surgical intervention, often fails to relieve all symptoms. Furthermore, anticholinergic drugs have significant adverse effects and may be medically contraindicated. Nocturia is a particularly disabling symptom of neurogenic bladder; by disrupting sleep patterns, it aggravates the chronic fatigue of MS, imposes serious demands on caregivers, and can lead to institutionalization. To evaluate a novel approach to the symptomatic management of nocturia in patients with MS, we have conducted a trial of desmopressin acetate (1-desamino-8-D-arginine vasopressin), a synthetic analogue of antidiuretic hormone. OBJECTIVE: To evaluate the efficacy and short-term safety of desmopressin therapy in the symptomatic treatment of nocturia in patients with MS. METHODS: Seventeen patients were enrolled in a double-blind, crossover trial of desmopressin administered at bedtime. Patients with both relapsing-remitting and chronic-progressive forms of MS were admitted. Night time voiding diaries were maintained for the 6 weeks of the trial; similarly, serum electrolyte levels and plasma osmolality were measured twice weekly and urinalyses and urine cultures were performed weekly during the trial. RESULTS: Desmopressin reduced the percentage of nights with nocturia in patients from 97% to 66%. The average number of episodes of nocturia per night in patients decreased from 2.35 to 1.09 and the maximum hours of sleep uninterrupted by nocturia increased from 3.74 to 5.77. These results were highly significant. Four of the 17 patients discontinued participation in the study after developing asymptomatic or minimally symptomatic hyponatremia. CONCLUSIONS: Desmopressin was found effective; no tolerance and only minimal adverse effects have been observed. Our results suggest that desmopressin, either alone or in combination with other therapeutic modalities, is effective in the symptomatic management of nocturia in patients with MS. The only adverse effect attributed to desmopressin was hyponatremia, which occurred in 4 of 17 patients and appeared to be dose related.     

Minocycline treatment and pseudotumor cerebri syndrome

We performed a quantitative investigation of arginine-vasopressin (AVP) immunopositive neurons in the suprachiasmatic nucleus (SCN), which is the endogenous clock of the brain of a patient with multiple system atrophy (MSA) who exhibited nocturnal polyuria associated with decreased urinary specific gravity and depression of nocturnal AVP secretion. Eleven age- and sex-matched subjects were used as controls. Although, the number of AVP-positive neurons was decreased in neither the supraoptic nucleus nor the paraventricular nucleus, the number of AVP-positive neurons in the SCN was decreased and gliosis was present in the SCN. The cytoplasmic area of AVP-immunopositive neurons in the SCN was smaller in the patient than in the control subjects. These findings raise the possibility that SCN is involved in MSA and the neurodegeneration in the SCN results in altered circadian rhythm of AVP secretion and nocturnal polyuria.     

Autonomic cardiovascular neuropathy in Sj?gren's syndrome. A controlled study

OBJECTIVE: To test patients with primary Sj?gren's syndrome (SS) for evidence of autonomic neuropathy. METHODS: Thirty-two patients with primary SS and 22 age and sex matched healthy individuals were asked specific questions about symptoms suggestive of autonomic neuropathy, and were subjected to a battery of 5 cardiovascular tests: response of blood pressure to sustained hand grip, Valsalva maneuver, heart rate response to deep breathing, and heart rate and blood pressure response to standing up. The chi-squared test with Yates' correction and 95% confidence intervals were used for statistical analysis of the results. RESULTS: Sixteen patients (50%) had symptoms of autonomic neuropathy when specifically asked versus none of the controls (p < 0.0005). The frequency of abnormal responses to the tests was 68.8% in patients and 12.7% in controls (p < 0.0001). Severe autonomic cardiovascular neuropathy was found in 87.5% of the patients but in none of the healthy individuals (p < 0.0001). CONCLUSION: Our results suggest that autonomic neuropathy is a feature of a significant portion of the SS population, and such patients should have appropriate evaluation. Similarly, patients with unexplained autonomic neuropathy should be investigated for evidence of SS.     

Immunohistochemical characterization of the differentiation state of basal cell carcinomas with special interest for infiltrating relapsing tumors

Persistence of nocturia after prostatic resection in healthy patients without symptoms referred to residual bladder instability and to pathological polyuria seems to be caused by an increased urine production at night. The more accreditate mechanism involved is the relevant decreased ADH secretion pattern which occurs at night. In our study, patients with nocturnal poliuria showed significantly low plasmatic vasopressin levels compared with a control group. The aim of this study was to evaluate whether the persistence of nocturia after prostatic resection in healthy patients, without symptoms referred due to residual bladder instability and important polyuria, could be due to a decrease or a lack of increase in antidiuretic hormone (ADH) nocturnal levels following increased urine production at night. Serum ADH, atrial natriuretic peptide (ANP) and osmolality were assessed at 4-h intervals in 12 patients complaining of residual nocturia (group A) and in a control group of 13 patients who had undergone a complete resolution of nocturia after prostate ablation (group B). In the 25 patients involved in the study (mean age 65.8 years), no significant differences were observed in the two groups concerning mean age (67.5 years for group A, 64 years for group B). Mean nocturnal urine volume (1080 +/- 490 ml) in group A patients was significantly higher than in group B (500 +/- 100 ml) (p < 0.001), while no significant differences were found in diurnal diuresis. Mean plasma vasopressin levels of the 12 patients showing an increased nocturnal micturition were found to be significantly lower at all 4-h intervals when compared with the control group (p < 0.05). Individual fluctuations in serum osmolality were slight and insignificant within the normal range in all patients. The diurnal variation of plasma atrial natriuretic peptide was within the reference limits for all subjects during the 24-h period. Our results lead us to believe that residual nocturia after prostatic resection seems to be caused by an increased urine production at night due to a decreased ADH secretion pattern.     

Urinary tract infections in infants, an insidious clinical picture

Three boys aged 4, 5 and 7 weeks drank poorly, vomited and were lethargic. There were metabolic disorders attributable to a urinary tract infection. Ultrasonography revealed anatomical anomalies. After antibiotic treatment and, if necessary, surgical correction, the patients recovered. Follow-up was uncomplicated except persisting polyuria in one of the patients. A urinary tract infection in young children is difficult to recognise because of the aspecific presenting symptoms. It can cause a severe metabolic disturbance in which hyponatraemia and hyperkalaemia develop (pseudohypoaldosteronism), combined with metabolic acidosis and polyuria. A high alertness for urinary tract infections in young children with these aspecific symptoms is needed as well as metabolic and urologic evaluation.     

Primary pulmonary hypertension

Justification of early treatment of nocturnal enuresis is founded in the negative psychological impact on the child. In fact nocturnal enuresis delays early autonomy and socialisation by decreasing in self-esteem and self-confidence. Nocturnal enuresis classification is the preliminary step to correct therapy. Enuresis must be classified as primary (never acquired nocturnal control) or secondary (at least 6 months of dry nights). A child is also classified as having monosymptomatic enuresis if she/he experienced only night wetting and symptomatic enuresis if she/he experienced night wetting associated with diurnal voiding symptoms (urinated > or = 7 times a day, urgency, damp pants, squatting, holding the perineum, sitting on one heel). Monosymptomatic patients must be treated with desmopressin nasal spray at the daily dose of 20 micrograms at bed time. If the reduction of at least the 50% of the basal number of the wet nights is not achieved, the dosage must be increased until 40 micrograms. For patients affected by rhinitis or asthma, desmopressin is now available in tablets. In symptomatic patients desmopressin therapy must be associated to oxybutinin (5 mg x 2). Therapy interruption must be gradual with desmopressin reduction of 10 micrograms every 30 days. In symptomatic patients oxybutinin must be introduced only at bed time. The efficacy of the drugs depends on the therapy length. The highest percentage of success is obtained if the treatment is protracted for at least six months. Antidepressants are also used for nocturnal enuresis especially imipramine. The dosage varies between 0.5-1.5 mg/ kg/daily. As plasmatic levels are achieved only in 30% of treated patients, a 3-5 fold increase in suggested. Nevertheless these levels result in near toxic threshold concentration. Sporadic treatment purposes include amytriptiline, diclofenac sodicum, viloxsazine and methilphenidate if giggle incontinence is present. Non responders may be treated with alarm. If after 16 weeks of treatment no success is obtained alarm use must be interrupted.     

Desmopressin versus indomethacin treatment in primary nocturnal enuresis and the role of prostaglandins

OBJECTIVES: To compare the efficacy of desmopressin and indomethacin and also determine the prostaglandin E2 (PGE2) concentrations in the patient and control groups. METHODS: Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks, during which they recorded wet and dry nights. After this period, the patients were divided into three groups that used desmopressin, indomethacin, or placebo for 4 weeks. The dosage of desmopressin (group A, n = 31 ) was 20 microg/day and the dosage of indomethacin (group B, n = 29) was 100 mg/day. The placebo group (group C) consisted of 25 patients. We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group. RESULTS: Treatment with desmopressin and indomethacin resulted in significantly more dry nights during the 4 weeks of observation than did placebo (P <0.005). The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group (P <0.01). In the total patient group, the mean serum and urine PGE2 concentrations were significantly different from the control group's serum and urine PGE2 concentrations (P <0.001). There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period (P <0.01). CONCLUSIONS: Desmopressin and indomethacin were found to be more effective than placebo. We conclude that prostaglandins have an important role in the pathophysiology of primary nocturnal enuresis.     

Nocturnal enuresis in children]

After allergic disorders, nocturnal enuresis is the most common chronic childhood condition. Recent research has yielded abundant new knowledge about the condition, especially about its aetiology and pathophysiology, and the psychological consequences. A hereditary background has been substantiated by the identification in genetic linkage studies of areas in chromosomes 12 and 13 that are manifestly associated with bedwetting, though genotype expression in the phenotype appears to be complex and heterogeneous. Pathophysiologically, findings in current intensive research suggest three interactive factors to be involved: (i) relative nocturnal polyuria, due to insufficient antidiuretic hormone release during sleep in pre-teenagers, and due to renal tubular dysfunction in adolescents and adults; (ii) reduced nocturnal bladder capacity, especially in the 33 per cent of cases which do not respond to desmopressin treatment; and (iii) the patient's inability to waken in response to signals from a full bladder. Recent findings have also confirmed previous reports that with very few exceptions bedwetting is not caused by psychological factors. On the contrary, the condition causes psychological problems manifested in reduced self-esteem, shame and guilt, though self-esteem is restored by successful treatment. Active treatment should be started as soon as the child is ready to receive it, the main options being an enuresis alarm, desmopressin, or a combination of the two. If reduced bladder capacity is suspected, treatment with a detrusor relaxant should be included.     

Disease, physician-patient contacts and work disability in a general practice

The frequency of Coronary Heart Disease symptoms (questionnaire from G. Rose) and some risk factors were recorded for 314 men in a general practice as part of a preventive screening programme. Simultaneously the number of physician-patient contacts and the total days of work disability were registered. The patients were divided into four social classes. There was a significant increase of symptoms of autonomic nervous disorder and hyperuricemia (p less than 0,025) as well as the number of smokers (p less than 0,001) with descending social class. The same trend was found with the frequency of physician-patient contacts and the total days of work disability (p less than 0,1). Patients with vegetative symptoms showed a mean of 7,2 physician-patient contacts and a work disability of 37,4 days per year. For patients with abnormal ECG findings the rates were 5,6 contacts and 33,4 days of disability per year. There was a significant difference in these rates compared to a control group.     

Association of relative nocturnal hypertension and autonomic neuropathy in insulin-dependent diabetic children

Twenty-four hour BP and heart rate measurements were carried out in fourteen newly diagnosed-, and in twenty-eight diabetics with 5-13 years of duration; and in eight healthy control children. Mean arterial BP rose at night in five-, fell slightly (less than 10%) in five- and fall markedly (more than 10%) in eighteen diabetics with longer duration of the disease. The diurnal-nocturnal difference of mean arterial pressure was significantly lower in the groups with nocturnal BP rise and slight nocturnal BP fall, compared to the control group (< 0.001; p < 0.01, respectively). The diurnal-nocturnal differences of heart rates were significantly lower in diabetics with relative "nocturnal hypertension" compared to the control group (p < 0.05). The presence of subclinical signs of diabetic autonomic neuropathy was significantly higher in patients with nocturnal BP rise and slight nocturnal BP fall compared to patients with marked nocturnal BP fall and newly diagnosed diabetics (chi squared p = 0.02 and p = 0.01, respectively). In conclusion, the prevalence of autonomic symptoms in diabetic children could be related to change in diurnal/nocturnal arterial BP, however longitudinal studies of ABPM are needed to define, whether patients with abnormal BP profiles are candidates for the development of diabetic vascular disease.     

Ambulatory blood pressure measurement in type-II diabetic patients with autonomic neuropathy

The aim of our study was to access the 24-hr ambulatory blood pressure (BP) in diabetic patients with autonomic neuropathy (AN). Twenty-two NIDDM patients without hypertension, being treated with sulfonylureas, were studied. The 24-hr ambulatory blood pressure recordings were performed using portable non-invasive automatic system. Autonomic neuropathy was assessed by standard cardiovascular reflex tests. There were ten patients with and 12 without AN, matched for age, body mass index, duration of diabetes and glycemic control. Mean BP increased at night in four of the subjects with AN and decreased in the remaining 18 patients. The group of subjects with nocturnal increases in BP had more severe autonomic nerve dysfunction compared with those with decreases in nocturnal BP. No significant difference between clinical and ambulatory day-time measurements was found. In three patients with AN after 5 weeks intensified therapy. 24-hr BP did not show any significant difference.     

A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder

OBJECTIVE: To assess whether there are common malfunctions (e.g. of the autonomic nervous system and smooth muscle) that underlie disorders of the urinary and gastrointestinal tracts by determining whether there is an increased prevalence (i) of urinary symptoms in patients with irritable bowel syndrome (IBS) and (ii) of gastrointestinal symptoms in patients with idiopathic detrusor instability (IDI). PATIENTS AND METHODS: Questionnaires were sent to patients with a diagnosis of IBS or IDI who were seen in the Departments of Gynaecology, Gastroenterology and Urology at the John Radcliffe and Churchill Hospitals, Oxford, during the 3 year period 1993-1995. The questionnaires were also distributed to control patients who were recruited from the day-surgery unit of the Churchill Hospital. Of 236 questionnaires sent out, 168 replies were analysed; 64 from patients with IBS, 49 from patients with detrusor instability and 55 from controls. The questionnaire included questions about micturition and defecatory behaviour (frequency, regularity, urgency, continence, pain, and ease in passing urine and stools). RESULTS: Patients with IBS were more likely to experience certain urinary symptoms than controls (nocturia, urgency and some forms of urinary urge incontinence) and patients with IDI were as likely as patients with IBS to experience gastrointestinal symptoms more frequently than controls. Control patients showed an unexpectedly high probability of experiencing many of the gastrointestinal and urinary symptoms. CONCLUSIONS: The frequent occurrence of symptoms in control patients makes the significance of the results less clear, but the association between certain symptoms of urinary tract disorder and patients with IBS, and of symptoms of gastrointestinal tract disorder with patients with IDI, suggests that they may share some common underlying dysfunction.     

Müllerianosis of the urinary bladder: clinical and immunohistochemical findings

BACKGROUND: Intranasal desmopressin has been used extensively to treat primary nocturnal enuresis. While it has proven to be a safe, effective agent for many who are affected by this condition, the potential for complications exists. OBJECTIVES: To report a case of severe hyponatremia associated with a generalized tonic-clonic seizure in a 10-year-old boy who had been receiving intranasal desmopressin nightly for nocturnal enuresis and to briefly review therapeutic options for nocturnal enuresis; and to present the role of desmopressin. SETTING: Georgetown University Medical Center, Washington, DC. INTERVENTION: Fluid restriction and intravenous isotonic saline solution with 5% dextrose was administered to raise the serum sodium level. OUTCOME: Prevention of further seizures with normalization of serum sodium levels without any obvious neurological sequelae. CONCLUSIONS: This case illustrates the importance of weighing the benefits and risks of intranasal desmopressin therapy.     

Tetanus toxin and botulinum A neurotoxin inhibit and at higher concentrations enhance noradrenaline outflow from particulate brain cortex in batch

Does long-term lithium treatment induce an irreversible renal damage, and does polyuria or changes in the calcium metabolism indicate this? To elucidate these questions GFR, diuresis, S-Ca, S-Mg, S-PTH and bone mineral content (photonabsorptiometry) were determined in 29 consecutive patients on long-term lithium therapy for 2.5--12 years and in 4 patients, who had been admitted to the Renal Clinic with lithium-induced polyuria. Only 1 of the patients had had a known lithium intoxication (S-Li > 2 mmol/l). None had a history of renal disease or significant analgesic consumption. In the consecutive series the GFR was not significantly reduced and no correlations were found between this parameter and the duration of lithium therapy, average S-Li, highest S-Li noted, diuresis or any of the calcium parameters. The morning diuresis was significantly increased in comparison with a control group with normal kidney function. 2 of the 4 polyuric patients had a decreased GFR, but in 1 case it was normalized on desmopressin supplementation. Renal biopsy in the patient with one S-Li of 2.35 and a low GFR in the consecutive series, and in 3 of the polyuric patients, revealed focal interstitial fibrosis and nephron atrophy. The mean S-Ca, S-Mg, S-PTH and bone mineral content were increased, but no significant intercorrelations between these parameters were found. Neither were any intercorrelations found between the calcium parameters and time on lithium therapy, average S-Li, highest S-Li noted or morning diuresis. In conclusion a relatively well-managed lithium therapy for up to 12.5 years does not seem to influence the GFR, even if renal biopsy in 4 of our patients revealed interstitial nephritis and data in the literature indicate a progressive interstitial nephritis. The present study did not support the proposition that polyuria is an alarming sign of pronounced renal lesion. Calcium metabolism is influenced by lithium therapy but from the clinical point of view no negative effects could be found. S-Ca should probably be checked regularly in patients on long-term lithium therapy.     

Primary polydipsia. Syndrome of inappropriate thirst

A patient with lifelong severe polyuria and polydipsia had normal serum antidiuretic hormone (ADH) levels and responded to water deprivation with a prompt increase in urine osmolality and maintenance of normal plasma osmolality (less than 290 mOsm/kg), despite extreme thirst. When treated with desmopressin acetate and allowed free access to water, she was able to reduce plasma osmolality below 270 mOsm/kg, and her compelling thirst disappeared. The disorder is interpreted to be the result of excessive fluid intake in response to a thirst stimulus that was not inhibited by normal plasma osmolality. This study indicates that osmoreceptor control of ADH secretion is normal. Continued administration of vasopressin has relieved the symptoms and has not resulted in water intoxication.     

Autonomic nervous function in progressive supranuclear palsy--comparison with Parkinson's disease and healthy controls

This study evaluated the autonomic nervous function in 6 patients with progressive supranuclear palsy (PSP). The autonomic nervous functions in PSP patients were compared with those in 17 patients of Parkinson's disease (PD) and 9 age-matched healthy control subjects. Results were that all PSP patients and 59% of PD patients had sympathetic skin response (SSR) abnormalities. Significant abnormalities in cardiovascular response observed in PD patients suggested the presence of sympathetic and parasympathetic disturbances. There were no significant differences between PSP patients and control subjects in cardiovascular responses. But some of PSP patients showed abnormal cardiovascular responses compared with the results from the control subjects. In PSP patients mild disturbances in cardiovascular responses and sudomotor dysfunction were suggested. We consider that the high incidence of SSR abnormality is at least partially related to the presence of disturbances in the frontal lobes.     

Extent of autonomic activation following cerebral ischemia is different in hypertensive and normotensive humans

OBJECTIVES: To evaluate whether the extent of autonomic activation following brain infarction differs between hypertensive and normotensive humans, and to investigate the role of the insular cortex for this sympathetic activation. DESIGN: Prospective, hospital-based study. SETTING: Department of Neurology of a university medical center. SUBJECTS: Forty-two patients with essential hypertension and 45 patients who were normotensive. MAIN OUTCOME MEASURES: Extent of autonomic activation following stroke as indicated by circadian blood pressure patterns, serum norepinephrine levels, and cardiovascular variables. RESULTS: Normotensive patients with insular infarction showed a significantly reduced circadian blood pressure variation and a higher frequency of nocturnal blood pressure increase compared with patients suffering from essential hypertension and insular stroke. These findings were also associated with higher serum norepinephrine concentrations and more frequent electrocardiographic abnormalities. No significant changes in these variables were seen between normotensive and hypertensive patients without insular involvement. CONCLUSIONS: Our findings suggest a difference in cortical control of autonomic function between hypertensive and normotensive patients after stroke and point to a possible role of the insular cortex in the pathogenesis of essential hypertension.     

A comparison of polydipsia prevalence among chronic psychiatric patients using three measurement approaches

Many previous prevalence studies of polydipsia (PD) have utilized single and often non-biologic measures. In this study we estimated prevalence using specific gravity of urine (SPGU), normalized diurnal weight gain (NDWG), and staff identification (staff ID). Agreement between these two biologic and one behavioral measure was assessed. A total of 572 psychiatric inpatients were assessed for SPGU and NDWG. Unit staff were asked to identify PD patients. Positive and negative PD groups were formed separately based on the SPGU, NDWG, and staff ID data. All three measures were collected on the same day. Prevalence data for the biologic measures varied. The estimate for PD by SPGU (< 1.009 cutoff) was higher (43.4% of sample) than that of NDWG (> 2.5%; 25.4%) or staff ID (21.4%). These prevalence rates did not change substantially after exclusion of medical causes of polyuria. Agreement, assessed by the kappa statistic, was uniformly low among the measures. Weak association between the measures reflects their multidetermined, nonspecific nature, and highlights the lack of a diagnostic standard in the field. The observed prevalence rates must be considered rough approximations. Associations between the measures and certain subject characteristics suggest the measures may identify different types of potential PD patients. These different types of patients are discussed, as are other issues in the measurement of PD. The data suggest estimates of PD are a function of the type of measure used as even biologic measures vary greatly.