Biomedical subjects
N M Resnick
Publications and source records attributed to N M Resnick.
Correlation between micturitional urethral pressure profile and pressure-flow criteria in bladder outlet obstruction.
PURPOSE: We correlate micturitional urethral pressure profilometry with pressure-flow diagnoses of outlet obstruction. MATERIALS AND METHODS: Urodynamic evaluation was done of 86 consecutive men with voiding symptoms. Obstruction criteria were a micturitional urethral pressure profile (MUPP) gradient greater than 5 cm. water, Schäfer's linear passive urethral resistance relation (PURR) greater than grade 1 and Abrams-Griffiths nomogram. RESULTS: Interpretable results were completed in 99% of the patients undergoing MUPP and 60% undergoing pressure-flow studies (p < 0.00001). MUPP diagnosis agreed with PURR (p = 0.0015) and Abrams-Griffiths nomogram results (p = 0.00004). MUPP gradients correlated well with PURR (r = 0.70, p < 0.00001). Using optimum cutoff values (11 cm. water), the sensitivity of MUPP was 83%, specificity 82% and positive predictive value 94%. CONCLUSIONS: MUPP correlates well with and yields interpretable results more often than pressure-flow studies.
Implications of the most bothersome prostatism symptom for clinical care and outcomes research.
OBJECTIVES: Because treatment of benign prostatic hyperplasia (BPH) is based largely on patients' symptoms, understanding and measuring the impact of these symptoms from the patient's perspective is critically important for clinical care. Such knowledge also is crucial for comparing patient-weighted outcomes because the increasing array of medical and surgical BPH treatments differ in their impact on specific symptoms. Our purpose was to determine the most bothersome symptom in older men seeking evaluation for symptomatic BPH and to examine whether age, comorbidity, or urodynamic evidence of prostatic obstruction were important covariates. DESIGN: Prospective evaluation of a consecutive series. SETTING: Veterans Affairs urology clinic. PARTICIPANTS: 115 men (age 69 +/- 6 years) presenting for initial evaluation of prostatism. MEASUREMENTS: Scores on standard symptom index and patients' reports of the most bothersome symptom. Bladder outlet obstruction was assessed by multichannel videourodynamic evaluation. RESULTS: An "irritative" symptom (frequency, urgency, or nocturia) was cited as most bothersome significantly more often than an "obstructive" symptom (weak stream, hesitancy, etc.) (53 vs. 35%, P < .05); older men were significantly more likely to name an irritative symptom as most bothersome (chi 2 for trend = 6.63, P < .025). Even among men with prostate obstruction, most cited an irritative symptom as the most bothersome, regardless of the severity of obstruction. These associations were not confounded by comorbid conditions or medications that independently may cause symptoms. CONCLUSIONS: Because irritative symptoms are most bothersome, have a diverse differential diagnosis, and do not respond as well to BPH treatment, neither providers nor researchers should rely solely on global assessments of symptom severity and bother in assessing men with voiding symptoms. Additional focus on individual symptom impact and etiology is needed, especially in older men.
Difficulty with holding urine among older persons in a geographically defined community: prevalence and correlates.
OBJECTIVE: The goal of this study was to estimate the prevalence and correlates of difficulty holding urine among a population of community-dwelling older people. DESIGN: Population-based cross-sectional study. SUBJECTS: A population census identified all residents aged 65 years and older residing in East Boston, Massachusetts, in 1982. MEASURES: Data collected via in-home interviews were used to estimate the prevalence of difficulty holding urine and to provide information regarding potential correlates of urinary difficulty. RESULTS: Of the 3809 study participants (85% response rate), 28% reported having "difficulty holding urine until they can get to a toilet" at least some of the time, and 8% reported difficulty "most" or "all of the time." Difficulty was associated with age and sex; 44% of women and 34% of men reported some difficulty (P < .001), and 9% of women and 6% of men (P < .001) reported difficulty most or all of the time. For respondents aged 65 to 74 years, 40% reported some difficulty, compared with 47% of those aged 85 and older (Ptrend < .001); difficulty most or all of the time was reported by 6% of those aged 65 to 74 and 12% of those aged 85 and older (Ptrend < .001). Difficulty holding urine was associated with important health and functional measures including depression, stroke, chronic cough, night awakening, fecal incontinence, problems with activities of daily living, decreased frequency and ease in getting out of the house, and poor self-perception of health. CONCLUSIONS: Difficulty holding urine is a prevalent condition among older people living in the community and is associated highly with a number of health conditions and functional problems.
Urinary incontinence and dementia: the perils of guilt by association.
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Continuous occlusion test to determine detrusor contractile performance.
PURPOSE: A study was conducted to determine the merits of the continuous occlusion test as a method of detrusor contractility assessment by comparing it with other stop tests and with contractility derived from pressure-flow analysis. MATERIALS AND METHODS: The continuous occlusion test was performed in elderly men by occluding the bladder outlet before the onset of a detrusor contraction and it was repeated to assess reproducibility. The magnitude of the isovolumetric contraction, maximum slope of the detrusor contraction, and duration of detrusor activation were determined. Voluntary and mechanical stop tests were performed during the mid voiding phase. Continuous occlusion test parameters were compared with the pressure-flow contractility parameters. RESULTS: The continuous occlusion test was evaluated in 159 patients. The maximum isovolumetric contraction pressure of the continuous occlusion test was significantly higher than that of the voluntary stop test (49 patients). Continuous occlusion test contractility parameters were reproducible. The maximum isovolumetric contraction pressure and the maximum slope of the detrusor contraction of the continuous occlusion test significantly correlated with the estimated maximum isovolumetric contraction pressure and estimated velocity of shortening (derived from pressure-flow), respectively (r = 0.79, p < 0.0001 and r = 0.385, p = 0.016, 39 patients). The watts factor was well correlated with maximum isovolumetric contraction pressure (r = 0.75, 39 patients). CONCLUSIONS: Our study suggests that the continuous occlusion test can be used as an effective alternative method of assessing detrusor contractility.
Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly.
OBJECTIVE: To determine the relative importance of fall characteristics, body habitus, and femoral bone mineral density (BMD) in predicting hip fracture in community-dwelling elderly. DESIGN: Prospective case-control study. SETTING: Community-based academic hospital. PARTICIPANTS: A total of 149 ambulatory, community-dwelling fallers (126 women, 23 men) aged 65 years and older, including 72 case patients (fallers with hip fracture) and 77 control fallers (fallers with no hip fracture). MAIN OUTCOME MEASURES: Fall characteristics, body habitus, femoral BMD. RESULTS: Significant and independent risk factors for hip fracture in both sexes were direction of the fall (adjusted odds ratio [OR], 5.7; 95% confidence interval [CI], 2.3 to 14.0; P < .001); femoral neck BMD (a decrease of 1 SD; adjusted OR, 2.7; 95% CI, 1.6 to 4.6; P < .001); potential energy of the fall (an increase of 1 SD; adjusted OR, 2.8; 95% CI, 1.5 to 5.2; P < .001); and body mass index (a decrease of 1 SD; adjusted OR, 2.2; 95% CI, 1.2 to 3.8; P < .01). Importantly, the OR for the fall direction was unaffected by the addition or removal of BMD from the model. CONCLUSIONS: We conclude that among elderly fallers--in most of whom hip BMD is already less than the fracture threshold--fall characteristics and body habitus are important risk factors for hip fracture and touch on a domain entirely missed by knowledge of BMD. These data suggest new targets for preventive therapy. In addition to the maintenance of bone density, reductions in fall severity (eg, by use of trochanteric padding or enhancement of muscle strength) may provide additional strategies for prevention of hip fracture in this age group.
Short-term variability of self report of incontinence in older persons.
OBJECTIVE: Virtually all estimates of the prevalence and incidence of incontinence in the community rely on self-reported continence status. The goal of this study was to assess the reliability of this measure in older adults. DESIGN: Telephone interviews administered approximately 2 weeks apart. SETTING: Community-based congregate living facility. PARTICIPANTS: A convenience sample of approximately 100 residents was contacted by letter; 48 of 51 (94%) who indicated their willingness to participate were interviewed. They included eight men and 40 women > 70 years old (79% > 80 years old), virtually all of whom were independent in basic ADLs and 83% of whom reported their health as good or excellent. MEASUREMENT: Responses to a structured questionnaire. MAIN RESULTS: The prevalence of urinary incontinence was 40% at baseline and 44% on re-interview; the prevalence of fecal incontinence was 17% on both occasions. All Spearman correlations for items related to urinary incontinence characteristics were between .80 and .86, except for a question related to stress incontinence (r = .62); correlations for fecal incontinence were .67-.69. CONCLUSION: Prevalence estimates of incontinence are stable over a 2-week period. However, the variability of individual responses, while relatively low, was within the range previously reported for estimates of incidence and remission rates of incontinence in community-dwelling elderly. This, variability should be taken into consideration when interpreting previous studies and designing future ones.
Urinary incontinence knowledge among community-dwelling people 65 years of age and older.
OBJECTIVES: We determined elderly persons' knowledge about the epidemiology and treatment of urinary incontinence (UI) as part of a preintervention survey for the Educational Demonstration of Urinary Continence Assessment and Treatment for the Elderly (EDUCATE). DESIGN: An intact-group pretest-posttest design was employed to measure the effects of multimethod educational interventions on the knowledge, attitudes, and practices of physicians and older people concerning UI. PARTICIPANTS: A random sample of community-dwelling people aged 65 years and older from two counties in Massachusetts was selected (n = 1,140). MEASUREMENT: A 14-item urinary incontinence quiz was developed from information presented in the AHCPR UI Guideline Panel's recommendations. Participants answers to the quiz were part of a 20-minute telephone interview. RESULTS: For nine of the fact items, the elderly respondents were more likely to give the correct answer than the incorrect answer. However, for only four of those nine did the percentage of correct responses exceed 50% (there were substantial proportions of "don't know" responses). For several fact items, those who were younger, female, or had more formal education were more likely to provide correct responses. CONCLUSIONS: There are substantial gaps in the knowledge of older persons about urinary incontinence, especially among men, those age 85 and older, and those with lower levels of education. These knowledge gaps may contribute to misinterpretation of symptoms and underreporting of symptoms to health care professionals. This pattern of findings indicates a greater need for community education on urinary incontinence.
Urinary incontinence in older adults.
A frequent and largely neglected problem, incontinence in the elderly can often be ameliorated or cured. Transient incontinence is usually secondary to intercurrent disease and thus should be addressed by treatment of that pathology. Established incontinence is most often due to detrusor hyperactivity. Behavioral intervention and bladder relaxants are management options.
Controversies in the diagnosis and management of benign prostatic hypertrophy.
The prevalence of BPH ensures a continuing need for internists to be aware of the issues regarding the evaluation and treatment of prostatism, while the developing role of nonoperative therapy and the growing recognition of the importance of patient preferences have opened the way for an expanded involvement of the primary care practitioner in the management of these patients. Prostatism remains a difficult clinical problem since many of the symptoms and diagnostic tests are nonspecific, especially in the elderly. Basic questions regarding the role of bladder outlet obstruction (BOO) in the development of symptoms and in predicting outcome from surgery await further study. Against this background of uncertainty, however, is the reassurance that the natural history of the process results in serious complications in only the minority of patients. Important work is under way that will incorporate quality of life outcomes, compare surgery with "watchful waiting," and randomize patients to surgical and nonsurgical treatments. In the interim, the internist may help patients with prostatism significantly by appreciating the natural history of the condition, treating the conditions that mimic or exacerbate it, understanding the clinical utility and limitations of current evaluation methods, becoming aware of the growing array of nonsurgical and minimal-surgery options, and assisting patients in weighing therapeutic risks and benefits with their concerns about symptoms.
A novel endopeptidase from Xenopus that recognizes alpha-helical secondary structure.
The magainin peptides of Xenopus laevis are broad-spectrum antimicrobial agents. Upon discharge from the skin glands, these basic, amphipathic peptides are each further processed at a single Xaa-Lys bond into half-peptides by a cosecreted protease. We describe the characterization and purification to homogeneity of this endopeptidase from Xenopus skin. The enzyme is a metalloprotease 110 kd in size. Analyses of substrate specificity revealed that the endopeptidase recognizes peptides that share the ability to adopt an amphipathic, alpha-helical motif composed of at least 12 residues, with one face strongly hydrophobic. Cleavage occurs on the amino side of a specific lysine that must be precisely positioned relative to the hydrophobic face of the alpha helix. This enzyme, which we propose to call "magaininase," represents a novel class of endopeptidases that hydrolyzes peptides on the basis of specific secondary structure rather than primary amino acid sequence.
Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy.
PURPOSE: The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women. PATIENTS AND METHODS: We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods. RESULTS: Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not. CONCLUSION: These data provide the first supportive evidence that long-term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy.
Evaluation of the causes and severity of geriatric incontinence. A critical appraisal.
The evaluation of urinary incontinence in the elderly differs from that in younger patients because of altered or nonspecific disease presentation, the different spectrum of pathophysiology, greater variation between individuals and, in some cases or settings, variable treatment goals. Evaluation must be multifactorial and extend beyond the genitourinary system, because many age-related conditions and the drugs used to treat them can cause or exacerbate urinary incontinence. Voiding records are a reliable measure of severity, although studies of their validity are still lacking. History-taking requires more time in this age group. Stress incontinence symptoms remain very sensitive, whereas obstructive symptoms fall in predictive value. Clinical algorithms based on a combination of symptoms and simple bedside examination and maneuvers may prove most useful in specific settings such as nursing homes. The targeting and interpretation of the physical examination must also change because of age-related conditions (e.g., BPH, atrophic vaginitis) and prevalent comorbid diseases, especially neurologic ones. The Q-tip, elevation, and pessary tests for stress incontinence offer little diagnostic or therapeutic information in the elderly. Routine laboratory tests should be performed to exclude reversible causes of urinary incontinence, while interpretation of the urinalysis must consider the prevalence of asymptomatic bacteriuria. No radiographic studies are routinely needed; bead-chain cystourethrography and IVU in particular probably offer little additional information. Voiding cystourethrography, although little studied, offers dynamic data that may be helpful, especially in evaluating outlet obstruction. Bedside cystometry is simple but may be insensitive to the most prevalent type of detrusor instability in the institutionalized elderly. Finally, multichannel urodynamic study is safe and feasible even in frail elderly patients and should be considered when empiric therapy is risky or has failed, complicated comorbidity exists, or surgery is anticipated.
Urinary incontinence--where do we stand and where do we go from here?
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Initial evaluation of the incontinent patient.
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Noninvasive diagnosis of the patient with complex incontinence.
Even in complex cases, the cause of incontinence can usually be discerned noninvasively. The author outlines one such approach, focusing on helpful diagnostic points that can be elicited without sophisticated urodynamic techniques.
'Senile' osteoporosis reconsidered.
Osteoporosis is a devastating, morbid, and costly condition whose ravages are felt most profoundly by women over age 70 years. Yet most research on its prevention and treatment has focused on perimenopausal women, although there are significant differences between perimenopausal and older women in factors related to bone mineral metabolism, rates of bone loss, the structural integrity of remaining bone, risk factors for fractures, and the types of fractures sustained. Currently recommended therapies, which slow bone loss in perimenopausal women, may be of less benefit for older women whose loss of bone has already slowed or ceased and whose remaining bone may be of inadequate quantity and quality to prevent fracture. Thus, the application of currently available modalities is unlikely to mitigate significantly the consequences of osteoporosis in this population. Further research is urgently needed, and some directions for future investigation are suggested.