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Biomedical subjects

N M Resnick

Publications and source records attributed to N M Resnick.

At least 37 records · Page 2Linked to original sources
PubMed1997

Initiation of voiding in humans: the nature and temporal relationship of urethral sphincter responses.

PURPOSE: The nature and sequence of events during the initiation phase of human micturition are unclear. Disagreement concerning the urethral sphincter response to detrusor contraction may stem from the functional extension of periurethral striated muscle to the bladder neck in many but not all individuals, and the methods used during conventional cystometry, in which individuals are asked to forestall urination for as long as possible (urgency voiding). We reasoned that by instructing individuals to void despite the lack of urgency (volitional voiding), and by stratifying results by whether striated muscle influence extended to the bladder neck, response of the proximal urethra might be more readily determined. MATERIALS AND METHODS: Using a triple microtip transducer catheter and a triple lumen fluid-filled catheter, we investigated 44 consecutive men and women with a variety of urodynamic findings, including 12 whose evaluation was normal. RESULTS: Despite the diversity of urodynamic diagnoses, once data were stratified as described, results were striking and uniform. The smooth muscle component of the bladder neck region contracted during the initiation of voiding in all subjects. Despite antecedent relaxation of the striated muscle sphincter, voiding did not begin until bladder pressure equaled or exceeded bladder neck pressure. CONCLUSIONS: Proximal urethral pressure increases in the initial phase of human micturition. These findings may have significant physiological, diagnostic and therapeutic implications.

Adult↗
PubMed1997

The prevalence of potentially remediable urinary incontinence in frail older people: a study using the Minimum Data Set.

OBJECTIVES: To use the Minimum Data Set (MDS) to describe the frequency and correlates of potentially treatable causes of urinary incontinence among a representative sample of American nursing home residents. To describe current management practices of urinary incontinence in the same population. DESIGN: Cross-sectional study using the dataset that was part of the Health Care Financing Administration (HCFA) evaluation of the MDS. SETTING: 270 Medicaid-certified nursing homes in 10 states. PARTICIPANTS: A total of 2014 nursing home residents 60 years or older (mean = 84.3 +/- 8.7), 75.5% women, 81.9% white, who lived in a nursing home during the fall of 1990 were randomly selected to sample a fixed number of residents for each facility based on facility size. MEASUREMENTS: Incontinence was defined as the presence of at least two episodes of urinary leakage per week in the previous 2 weeks. Management techniques (toileting, pads/briefs, catheters) were those listed in the MDS. Potentially remediable causes of urinary incontinence available in the MDS were: medications (antipsychotics, antidepressants, and antianxiety/hypnotics); congestive heart failure; diabetes mellitus; pedal edema; delirium; depression; and impairments in activities of daily living (ADLs) (transferring, locomotion, dressing, toileting; bedrails; trunk restraints; and chair restraints). RESULTS: Forty-nine percent of residents were incontinent. Of these, 84.0% were managed by pads/briefs, 38.7% by scheduled toileting, 3.5% by indwelling catheter, and 1.2% by external catheter. Of the potentially reversible causes, bivariate analysis revealed associations (P < .1) with use of antidepressants, antipsychotics, and antianxiety/hypnotics; delirium; bedrails; trunk restraints; chair restraints; and ADL impairment. Dementia was also associated with incontinence (P < .1). Multivariate analysis revealed that urinary incontinence was independently associated with impairment in ADLs (OR = 4.2; CI = 3.2,5.6), dementia (OR = 2.3;CI = 1.8,3.0), restraints-trunk (OR = 1.7; CI = 1.5,2.0), chair (OR = 1.4; CI = 1.2,1.6), bedrails (OR = 1.3; CI = 1.1,1.5), and use of antianxiety/hypnotic medications (OR = .7;CI = .5,1.0) (all P < .04). CONCLUSIONS: Current management practices for urinary incontinence are inconsistent with advocated guidelines. These data also confirm the association between incontinence and several potentially remediable conditions and suggest that, even in the nursing home setting, urinary incontinence may respond to efforts to improve conditions not directly related to bladder function. This study underscores the need to examine the impact on urinary incontinence of strategies to address such conditions.

Activities of Daily Living↗
PubMed1997

Structural basis of geriatric voiding dysfunction. V. Standardized protocols for routine ultrastructural study and diagnosis of endoscopic detrusor biopsies.

PURPOSE: Previous ultrastructural and clinical studies have established criteria for distinctive ultrastructural patterns in the normal, overactive, hypocontractile and obstructed detrusor of the elderly. This study was conducted to standardize procedures of detrusor biopsy processing, identify and address pitfalls and difficulties in applying the criteria to routine evaluation of biopsies in the surgical pathology laboratory, verify reproducibility of ultrastructural observations and diagnosis in biopsies from different sites in the bladder wall, and develop a standard approach to routine ultrastructural evaluation of the biopsy. MATERIALS AND METHODS: Blinded to clinical information, 25 randomly selected detrusor biopsies were evaluated by a pathologist with prior knowledge of electron microscopy but none of detrusor ultrastructure. The observations and diagnoses made were subsequently correlated with urodynamic bladder behavior evaluated comprehensively before biopsy. Biopsies from different sites of 4 detrusors and specimen samples of multiple sites from a bladder obtained at autopsy were also blindly assessed to determine the reproducibility of single site biopsies. RESULTS: Essential parameters of all criteria were verified. Potential pitfalls and sources of difficulty in some were identified and corrected to refine the criteria. Diagnoses were reproducible in all 5 detrusors with multiple site biopsies. Detailed protocols for electron microscopic study and diagnosis of dysfunctional detrusor biopsies were generated. CONCLUSIONS: The protocols eliminate problems that may be encountered in ultrastructural evaluation of biopsies from dysfunctional detrusors, and have been applied readily and successfully in our subsequent studies. Uniformity of structural organization of detrusor allows valid application of the protocols and study criteria to small biopsies obtained from different sites in the bladder wall.

Aged↗
PubMed1997

Structural basis of geriatric voiding dysfunction. VI. Validation and update of diagnostic criteria in 71 detrusor biopsies.

PURPOSE: Refined criteria of distinctive patterns of detrusor ultrastructure in geriatric voiding dysfunctions have been developed as standard protocols for pathological evaluation of detrusor biopsies. This study was performed to test completeness and routine applicability of these protocols, corroborate our original ultrastructural/urodynamic correlations in larger material and identify subtle correlations that may have been elusive in our original study of 35 cases. MATERIALS AND METHODS: A total of 71 endoscopic detrusor biopsies was obtained from 44 elderly subjects grouped following comprehensive clinical and urodynamic evaluation into those with normal aging bladder, detrusor overactivity, impaired detrusor contractility, bladder outlet obstruction or a combination. Biopsies were evaluated ultrastructurally and randomly, and blinded to clinical information. Using standard protocols the primary ultrastructural pattern(s) was identified, additional auxiliary features were recorded and pathological diagnoses were made. Biopsies were grouped accordingly, still blindly, and correlated with urodynamic groups determined independently prior to biopsy. RESULTS: Our observations confirmed that the standard protocols are complete and readily applicable to routine ultrastructural evaluation of detrusor biopsies. They corroborated our previously reported ultrastructural/urodynamic matching of the biopsies in every case and revealed new constant features of the normally aging detrusor. We identified ultrastructural correlates distinguishing moderate and severe from mild or borderline (but not moderate from severe) impairment of detrusor contractility. CONCLUSIONS: The proposed protocols are consistently applicable to the routine pathological diagnosis of geriatric voiding dysfunction in detrusor biopsies. A diagnostic algorithm was developed to serve as a practical guide for making such diagnoses, and gaining insights into the pathophysiology of geriatric and possibly other voiding dysfunctions.

Aged↗
PubMed1997

Structural basis of geriatric voiding dysfunction. VII. Prospective ultrastructural/urodynamic evaluation of its natural evolution.

PURPOSE: In cross-sectional studies ultrastructure of geriatric detrusors consistently correlates with their urodynamic behavior. This study was conducted to determine whether the ultrastructural observations were stable with time, changed in concert with urodynamic change and predicted or preceded such change. MATERIALS AND METHODS: Twenty-three elderly subjects underwent clinical and urodynamic evaluation plus endoscopic detrusor biopsy with ultrastructural study. The subjects were grouped according to urodynamic status. All were followed for up to 67 months and the same studies were repeated once in 19 (mean followup 27 months) and twice in 4 (mean followup 42 months) subjects. Biopsies (50) were classified according to their distinctive ultrastructural patterns without knowledge of clinical and urodynamic information. After all cases were studied, ultrastructural and urodynamic observations were correlated. RESULTS: Ultrastructural and urodynamic diagnoses matched in all 23 cases at baseline. After 1 followup period both diagnoses were unchanged in 16 (70%) and both changed concordantly in 7 (30%), as expressed by progression of ultrastructural features with new development or increased severity of the associated dysfunction. Auxiliary ultrastructural features underwent some change as well. One of 4 subjects with 2 followup studies had the same ultrastructural and urodynamic diagnoses, while in the other 3 complete dysjunction pattern developed with detrusor overactivity after the first followup and both remained unchanged after the second study. CONCLUSIONS: Ultrastructure of the detrusor corresponds perfectly to its urodynamic behavior with time whether the latter remains stable or changes. Although we cannot as yet determine the temporal sequence of changes in detrusor ultrastructure and function, the change in the former is clearly not a mere result of long-standing change in the latter. Auxiliary ultrastructural features may represent transitional changes that precede development of the ultrastructural patterns and the corresponding urodynamic abnormalities.

Aged↗
PubMed1997

Magnetic resonance imaging of the lower urinary tract.

Magnetic resonance imaging with its excellent contrast resolution and direct multiplanar imaging capacity, has become a valuable tool to improve understanding of lower urinary tract function and pelvic floor physiology. Review of the current English language literature shows that the domain of magnetic resonance imaging is research. In comparison with other imaging techniques, magnetic resonance imaging has been shown to yield better soft tissue differentiation and anatomic resolution. Newer techniques also allow some form of dynamic imaging.

Female↗
PubMed1996

Evaluating a national assessment strategy for urinary incontinence in nursing home residents: reliability of the minimum data set and validity of the resident assessment protocol.

Evaluation of 1 million incontinent American nursing home residents is hampered by both failure to detect incontinence and logistical barriers to diagnostic testing. The nationally mandated Minimum Data Set (MDS) and Resident Assessment Protocol (RAP) were devised to address these deficiencies. Although both instruments are also used in at least 18 other countries, neither has been evaluated. Our goal was to determine the reliability of the MDS and the accuracy of the RAP in predicting the lower urinary tract cause of incontinence. We determined interrater reliability for the 13 MDS items related to urinary incontinence in 123 randomly selected residents of 13 nursing homes in 5 states; forms were completed blindly by 2 nurses from each facility who were trained for a day. The RAP was assessed in 102 representative institutionalized women by blinded evaluation of its diagnostic accuracy compared with the multichannel videourodynamic criterion standard. For the MDS, interrater reliability for incontinence of all grades was excellent (weighted kappa correlation coefficient = 0.90), although reliability was greater at the extremes of measurement than for incontinence of intermediate severity. With the exception of delirium, correlations for the 11 MDS items related to incontinence were 0.65-0.96; for 6 items, correlations were > or = 0.8. The diagnostic accuracy of the RAP, successfully administered to 80% of women, was 70%. The accuracy of the nearly identical algorithm that formed the basis for the RAP was 84%. Importantly, serious misclassifications were not observed for either the RAP or the algorithm. Although its definitions should be modified slightly, the MDS appears to be feasible and reliable when administered by trained staff. In women, the diagnostic accuracy and safety of the RAP are good-particularly when administered as instructed-but the original, sex-specific algorithm is preferable. Together, the MDS and modified RAP provide a useful, stepwise, and non-urodynamically based strategy to guide evaluation and therapy of incontinence in this setting.

Aged↗
PubMed1996

Misdiagnosis of urinary incontinence in nursing home women: prevalence and a proposed solution.

Because of the high prevalence of detrusor hyperactivity with impaired contractility (DHIC) in incontinent institutionalized women, we postulated that: 1) single-channel cystometry, the most commonly used diagnostic test, would be inadequate when used alone but that 2) its accuracy could be greatly enhanced by combining it with a previously-performed stress test. To test the hypothesis, we used blinded comparison of a clinical stress test and single-channel cystometry with multichannel videourodynamic evaluation (criterion standard), a strategy designed a priori. Subjects were 97 incontinent women who were considered representative of incontinent nursing home women nationally. With cystometry alone, 9 of 37 women with DHIC (24%) were misdiagnosed as stress-incontinent vs. 1 of 25 with DH (P = .03). In each case, misdiagnosis was due to failure to recognize low-pressure involuntary bladder contractions. Combining cystometry with the stress test improved diagnostic accuracy markedly. Of the 77% of women in whom the results of both tests were congruent, all were correctly classified. When results of the two tests were discordant, neither was superior. Significantly, no woman with stress incontinence was missed by the two-test strategy, nor was anyone with detrusor hyperactivity misclassified. We conclude that in institutionalized elderly women, DHIC commonly mimics other types of urinary tract dysfunction. Thus, single-channel cystometry alone is an inadequate diagnostic test in this population. However, a strategy that combines cystometry with a clinical stress test can correctly classify the majority of such women and identify those in whom the diagnosis is less secure. Use of this simple strategy would facilitate correct diagnosis and initial treatment of most institutionalized women without referral, and also enrich the referred population with those most likely to benefit. Such an approach could significantly improve the approach to this costly and morbid condition.

Aged↗
PubMed1996

Geriatric incontinence.

Regardless of age, mobility, mentation, or institutionalization, incontinence is never normal. By attenuating physiologic reserve, aging increases the likelihood of becoming incontinent in the setting of additional physiologic, pharmacologic, or pathologic insults. Because many of these problems lie outside the urinary tract, so too must the diagnostic and therapeutic focus. Such a strategy, however, coupled with a multifactorial, creative, persistent, and optimistic approach, increases the chances of a successful outcome and generally rewards patient and physician alike.

Aged↗
PubMed1995

Gene therapeutic approach to primary and metastatic brain tumors: I. CD44 variant pre-RNA alternative splicing as a CEPT control element.

Our laboratory and others have shown alternative splicing of up to ten exons at a discrete extracellular site to be primarily responsible for the generation of CD44 variant (CD44v) isoforms. Based on clear differences in the expression of these CD44v isoforms between normal and malignant tissues, we believe that elucidation of the mechanisms underlying the regulation of CD44 alternative splicing may provide a new gene therapeutic targeting approach based on CD44 pre-mRNA processing in vivo. This strategy incorporates utilization of CD44 alternative splicing control elements into a chimeric enzyme/prodrug therapy (CEPT), a novel modification of the virus-directed enzyme/prodrug therapy (VDEPT) approach for the treatment of brain metastases from tumors of systemic origin. As initial steps towards the development of a gene therapeutic approach based on targeting tumor cell expression of specific CD44v alternatively spliced isoforms, we have: (1) developed a novel in vivo assay system that allows the rapid analyses of potentially therapeutic CD44 alternative splicing minigene constructs; and (2) cloned the E. coli cytosine deaminase (CD) gene and fused its enzymatically active domain to alternatively spliced CD44 exons (CD44/CD). Deamination of cytosine by this CD44/CD chimeric fusion protein is demonstrated in E. coli cell lysates to be equal to that of wild type cytosine deaminase.

Alternative Splicing↗
PubMed1995

Gene therapeutic approaches to primary and metastatic brain tumors: II. ribozyme-mediated suppression of CD44 expression.

Glioblastomas are highly invasive intracerebral tumors that are known to express the CD44 cell adhesion molecule. Human glioma cell adhesion and invasion in vitro may in part be mediated by the interaction of CD44 with extracellular matrix proteins. To suppress the growth and invasive effects of CD44 expression on primary brain tumors we have designed two hammerhead ribozymes as potential gene therapeutic agents. Both ribozymes designed to target exon 2 of CD44 exhibited in vitro cleavage of in vitro transcribed CD44s and CD44R1 RNAs. The anti-CD44 effect of these ribozymes results from directed RNA cleavage, requiring both a target sequence and an appropriate catalytic center. Further, following transient transfection of one of these ribozymes into the SNB-19 glioma cell line, significant in vivo cleavage activity against cellular CD44 transcripts was demonstrated by flow cytometrical analysis. These preliminary results suggest that CD44-directed hammerhead ribozymes may be useful as gene therapeutic agents.

Base Sequence↗