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PubMed2005

Loss of chondrolabral containment of the glenohumeral joint in atraumatic posteroinferior multidirectional instability.

BACKGROUND: Although the cause of posteroinferior instability of the shoulder has not been fully defined, glenoid version can be more completely measured when chondrolabral structures are included because conformity and containment of the glenohumeral joint are integral functions of both the articular cartilage and the labrum. The purpose of this study was to use magnetic resonance imaging-arthrography to evaluate the chondrolabral containment of the glenohumeral joint in patients with atraumatic posteroinferior multidirectional instability of the shoulder. METHODS: We evaluated four measurements (osseous and chondrolabral glenoid version, labral height, and glenoid depth) on T2-weighted axial magnetic resonance-arthrography images of thirty-three shoulders with atraumatic posteroinferior multidirectional instability. Shoulders with a documented labral tear were excluded. The measurements were compared with those of thirty-three age-matched controls without glenohumeral pathology. The angles of version of the osseous and chondrolabral portions of the glenoid were measured in three consecutive planes (superior 25%, middle 50%, and inferior 75% in relation to the superior lip of the glenoid) perpendicular to the long axis of the glenoid. RESULTS: The shoulders with posteroinferior instability had greater retroversion of both the osseous and the chondrolabral portion of the glenoid in the middle and inferior planes. The chondrolabral portion of the glenoid had more retroversion than the osseous portion in the inferior plane. The height of the posterior portion of the labrum was decreased in the inferior plane in the shoulders with instability. Glenoid depth in the middle and inferior planes was significantly shallower in the shoulders with instability. CONCLUSIONS: Loss of containment in the chondrolabral portion of the glenoid in the middle and inferior planes is a consistent finding in shoulders with atraumatic posteroinferior multidirectional instability and is associated with loss of posterior labral height. It is unclear whether the retroversion of the posteroinferior aspect of the labrum is a cause or a consequence of atraumatic posteroinferior multidirectional instability, but this factor should be considered during surgical repair.

Adult↗
PubMed2006

Risk factors for recurrence of shoulder instability after arthroscopic Bankart repair.

BACKGROUND: The higher failure rates reported with arthroscopic stabilization of traumatic, recurrent anterior shoulder instability compared with open stabilization remain a concern. The purpose of this study was to evaluate the outcomes of arthroscopic Bankart repairs with the use of suture anchors and to identify risk factors related to postoperative recurrence of shoulder instability. METHODS: Ninety-one consecutive patients underwent arthroscopic stabilization for recurrent anterior traumatic shoulder instability. The mean age (and standard deviation) at the time of surgery was 26.4 +/- 5.4 years. Seventy-one patients were male. Seventy-nine patients were involved in sports (forty, in high-risk sports). Capsulolabral reattachment and capsule retensioning was performed with use of absorbable suture anchors (mean, 4.3 anchors; range, two to seven anchors). All patients were prospectively followed, and, at the time of the last review, the patients were examined and assessed functionally by independent observers. RESULTS: At a mean follow-up of thirty-six months, fourteen patients (15.3%) experienced recurrent instability: six sustained a frank dislocation and eight reported a subluxation. The mean delay to recurrence was 17.6 months. The risk of postoperative recurrence was significantly related to the presence of a bone defect, either on the glenoid side (a glenoid compression-fracture; p = 0.01) or on the humeral side (a large Hill-Sachs lesion; p = 0.05). By contrast, a glenoid separation-fracture was not associated with postoperative recurrent dislocation or subluxation. Recurrence of instability was significantly higher in patients with inferior shoulder hyperlaxity (p = 0.03) and/or anterior shoulder hyperlaxity (p = 0.01). On multivariate analysis, the presence of glenoid bone loss and inferior hyperlaxity led to a 75% recurrence rate (p < 0.001). Lastly, the number of suture-anchors was critical: patients who had three anchors or fewer were at higher risk for recurrent instability (p = 0.03). CONCLUSIONS: In the treatment of traumatic recurrent anterior shoulder instability, patients with bone loss or with shoulder hyperlaxity are at risk for recurrent instability after arthroscopic Bankart repair. At least four anchor points should be used to obtain secure shoulder stabilization.

Adolescent↗
PubMed2006

[Microsatellite instability among patients with colorectal cancer].

BACKGROUND: In patients with colorectal carcinoma, insertions or deletions of short sequences of DNA, a phenomenon called microsatellite instability, are observed. AIM: To look for microsatellite instability and mutations of MLH1 and MSH2 gene mutations in patients with colorectal carcinoma. MATERIAL AND METHODS: Ten patients with sporadic colorectal carcinoma and 31 patients fulfilling criteria for hereditary nonpolyposis colon cancer (HNPCC), aged 9 to 70 years, were studied. Microsatellite instability was studied in samples of tumor and peripheral blood mononuclear cell DNA. Six markers were amplified by polymerase chain reaction and capillary electrophoresis. In samples with microsatellite instability, mutations of MLH1 and MSH2 genes were studied by direct sequencing. RESULTS: Thirty four percent of patients had microsatellite instability and among these, 76% had a high degree of instability. BAT40 marker had the higher frequency of instability. No mutations for MLH1 and MSH2 genes were observed. However a new polymorphism, C399T, was identified in exon 3 of MSH2 gene. This polymorphism was observed both in patients with sporadic colorectal carcinoma and patients with HNPCC. CONCLUSIONS: There is a high frequency of microsatellite instability among patients with colorectal cancer. A new polymorphism, not previously reported, was identified in MSH2 gene.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Soft tissue stabilization in the management of chronic scapholunate instability without osteoarthritis. A 15-year series.

Management of chronic scapholunate instability without osteoarthritis remains controversial. Some surgeons favor partial wrist arthrodesis; others, soft tissue stabilization. Many techniques for soft tissue repair have been described but with few or unpredictable results. We reviewed all our cases of scapholunate instability without osteoarthritis treated by soft tissue stabilization. Since 1979, 37 soft tissue stabilization procedures have been performed to correct dynamic (25) or static (12) scapholunate instability without osteoarthritis. The average time from injury to surgical treatment was 7.2 mos. (range 0.25 to 36 mos.). Three cases were treated within the first month of injury. The choice of repair was determined intraoperatively. The scaphoid shift must be easily reducible to make the case eligible for soft tissue repair. The scapholunate ligament was usually disrupted from palmar to dorsal, and the average amount of disruption was 74%. When scapholunate ligament remnants were of sufficient quality, secondary repair was performed; but if not, ligament reconstruction using tendon grafts or capsulodesis was performed. The procedures used were secondary ligamentous repair in 16 (by direct suture, reinsertion using anchor and/or transosseous reattachment), ligament reconstruction using tendon grafts in 6, capsulodesis in 7 and a combination of these procedures in 8. The mean follow-up was 27 mos. (range 2 to 62 mos.). Postoperatively, there was an 83% decrease in pain. The average wrist motion was 60 degrees extension, 47 degrees flexion, 18 degrees radial deviation and 28 degrees ulnar deviation (92%, 84%, 106% and 88% of preoperative values and 88%, 75%, 78% and 76% of the uninvolved wrists, respectively), and the grip strength was 28 kg (117% of preoperative value and 78% of the uninvolved wrists). On roentgenograms, the mean static scapholunate distance was 4.2 mm (a 26% loss of reduction compared to the early postoperative gap), but scapholunate and radiolunate angles were within normal values (58 degrees and 9 degrees, respectively). At follow-up, one patient presenting a small zone of chondromalacia on the scaphoid at the time of secondary ligamentous repair developed severe radioscaphoid arthritis 15 months postoperatively. The results were further assessed according to the form of instability, delay before surgery, severity of disruption and type of repair. Patients with static instability showed worse clinical and radiological findings than those with dynamic instability. Surgical delay did not influence the outcome. The more severe the ligament disruption was, the poorer were the results. All types of repair had a comparable outcome except those treated by ligament reconstruction using tendon grafts. The results in the latter group were unsatisfactory in terms of motion, grip strength and radiological findings. This technique has been abandoned by the group. In conclusion, soft tissue stabilization is part of the armamentarium in the management of reducible chronic scapholunate instability without osteoarthritis. Ligament reconstruction using tendon grafts gave, in our hands, unsatisfactory results. Otherwise, all types of repair achieved a relatively pain-free wrist, with acceptable motion, grip strength, scapholunate and radiolunate angles but with a wider than normal static scapholunate distance. A longer follow-up is needed to assess the effect of this abnormal gap. Factors that favorably affected the outcome were: dynamic type of instability and partial disruption of the ligament.

Adolescent↗
PubMed2003

[Shoulder arthroplasty for osteoarthritis after prior surgery for anterior instability: a report of 27 cases].

PURPOSE OF THE STUDY: The purpose of this study was to analyze the natural history of shoulder osteoarthritis secondary to prior surgery for anterior instability, to evaluate clinical and radiological results of shoulder prosthesis, and to compare results with reports in the literature. MATERIAL AND METHODS: Twenty-seven shoulder prostheses (Aequalis) were implanted in patients with osteoarthritis of the shoulder after prior instability surgery. These shoulders were reviewed retrospectively at a mean follow-up of 46 months (range 24-48). Prior surgery had been performed with coracoid block in two-thirds of the shoulders and with soft-tissue procedures in one-third. Twenty-four shoulders had had one instability procedure, several procedures had been performed in three. The Constant score was used to assess clinical status preoperatively and at last follow-up. Male gender predominated (16/27), and mean age at first dislocation was 31.6 years (4 patients experienced their first dislocation after the age of 60 years). The patients had a mean 18.2 dislocations. The natural history of osteoarthritis was long: 24.2 years on the average. Mean age at arthroplasty was 55.8 years. The preoperative images demonstrated an iatrogenic factor in 5 shoulders and constructive osteoarthitis in 24. Posterior glenoid wear was observed in 24% of the cases, fatty degeneration of the subscapularis in 45% and full-thickness tears of the supraspinatus in 4 cases. The anterior scar tissue was released and implants were positioned anatomically in 26 cases. Total arthroplasty was used for 21 shoulders and a humeral prosthesis for 6. RESULTS: There were five complications including three anterior prosthetic instability, all three in patients who were over 60 years of age at their first instability surgery (one of these three patients required revision arthroplasty). Outcome was good or excellent in 56% of the shoulder with a mean weighted Constant score of 83%: mean gain in pain score=8.3 points, in anterior elevation=51 degrees, in external rotation=33.5 degrees. The type of prior instability surgery and preoperative active external rotation had no determining effect on outcome. Factors correlated significantly with outcome were fatty degeneration of the rotator cuff muscles, particularly the subscapularis. DISCUSSION: Osteoarthritis of the shoulder has a long natural history, 26 years in our patients excepting those whose first dislocation occurred after the age of 60 years. Posterior glenoid wear, described by others, was only found in 24% of the shoulders in this series. Surgical dissection and release of anterior scar tissue was difficult. The overall results of arthroplasty were good and were correlated with fatty degeneration of the rotator cuff muscles, particularly the subscapularis, but not with the type of instability surgery. These results were less satisfactory than reported in series of arthroplasty for primary centred osteoarthritis: complications occurred in 18% of the shoulders with three cases of anterior dislocation. Unlike reports of arthroplasty after instability surgery where many of the patients had several operations, overall results in our series were not compromised by a large number of multiple interventions.

Adolescent↗
PubMed1984

Prevention of congenital dislocation of the hip. The Swedish experience of neonatal treatment of hip joint instability.

The extensive work on early diagnosis and treatment of CDH (in the broad sense of this term) in Sweden has formed the basis of our present organization of prevention of hip dislocation. Practically all children are born in hospital, at present about 93,000 per year (1980). Routine examination of the hip joints has been included in the check-ups of newborns since the beginning of the 1950's. The centralization of obstetrics, especially during the last decade, has facilitated the organization of these examinations by paediatric consultants in all obstetric departments. All cases of hip joint instability are recorded, and during the last few years the frequency has been about 12 per thousand, probably with some over-diagnosis due to registration of uncertain cases. All definite cases of hip instability have been treated immediately at the orthopaedic departments. A study of a series of untreated newborns with transient instability has shown that the majority, but not all, will develop normal hip joints without treatment. This has been one reason for the recommendation to treat all unequivocal cases of hip instability. The present organization of examination and treatment is described. Detailed and practical instructions for the examination and treatment are given. Follow-ups of children treated for hip instability in the neonatal period are reported. It has been found that in practically all these patients anatomically normal hip joints are achieved by means of correct and carefully followed up treatment. The findings in 65 patients with neonatal hip instability in whom the treatment was unsuccessful or inadequate have underlined the importance of a strict treatment schedule, experienced doctors and detailed information to the parents. The effect of diagnosis and treatment of hip instability neonatally on the frequency of late-diagnosed cases of CDH was studied by recording all late-diagnosed cases at all orthopaedic departments. It was clear from the latter study that instability of the hip in newborns represents "preluxation" and that the treatment of this can prevent later dislocation. Dislocation of the hip joint in newborn infants is very unusual. Nowadays it is rare even after the neonatal period--in recent years only 12% of the late-diagnosed CDH cases between 1 and 6 months of age at diagnosis. However, the total number of late-diagnosed cases in the whole country has not decreased by more than 50% compared with the period prior to the introduction of hip examination of newborns.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1994

[Instability of the shoulder joint in the athlete].

In all shoulder instabilities it is very important to classify the type of instability precisely in order to choose the right form of therapy and predict the results. The acronyms TUBS, which means traumatic instability, unidirectional, Bankart lesion, and good response to surgery, and AMBRI, which means atraumatic aetiology, multidirectional, and good for rehabilitation, represent the complete range of possible instabilities. We discuss the subtypes in the differentiation of various instabilities and the different causes and pathologies for instability, the clinical and radiological tests possible, and the different surgical treatment options, as well as the results in the literature. A modification of the Bankart procedure and the arthroscopic Caspari capsulorrhaphy procedure for traumatic instabilities are described. The capsular T-shift by Neer and Foster is explained as a surgical treatment for multidirectional instability.

Arthroscopes↗
PubMed1994

Operative treatment of posterolateral instability of the knee.

Acute and chronic posterolateral instability is often associated with cruciate injury. The results of surgical reconstructions for acute posterolateral instability are better than for chronic posterolateral instability. The authors recommend acute reconstruction of posterolateral injury when possible. In either acute or chronic instability, we first reconstruct any associated cruciate injury, and then expose the posterolateral corner through an open lateral incision. The authors believe that the LCL, popliteal attachment to the tibia, and the popliteofibular ligament are the most important posterolateral static stabilizers. Accordingly, we attempt to anatomically repair or reconstruct these structures in acute and chronic posterolateral instability. In acute injury the authors first attempt direct repair, advancement and recession, or augmentation of the LCL, the popliteal attachment to the fibula and popliteofibular ligament. Occasionally, reconstruction with patellar tendon autografts or allografts, or achilles allografts will be needed. In the patient with chronic posterolateral instability and varus alignment, a proximal, valgus tibial osteotomy is performed. Additional posterolateral reconstruction can be performed on a staged basis. In the patient with chronic posterolateral instability and valgus alignment, direct repair, advancement and recession, or augmentation can be attempted, but reconstruction with patellar tendon or achilles allograft often will be required. Proper anatomic reconstruction of all injured structures is recommended to achieve the best results in the operative treatment of posterolateral instability.

Anterior Cruciate Ligament↗
PubMed1998

[Shoulder joint instability after primary arthroplasty].

Instability is one of the most common complications after shoulder arthroplasty. The literature cites subluxation or luxation to occur between 0% and 38% in various studies. Instabilities may present either as subluxation or frank dislocation, and may be directed in an anterior, posterior, inferior or, depending on the state of the rotator cuff, cranial direction. The stability of any shoulder joint is given by the balance of the muscles directing the forces around the shoulder joint in association with the passive stabilizers of the shoulder joint capsule as well as the bony contours between glenoid and humeral head. Any disturbance of this delicate balance will lead the shoulder into instability, particular so if bony erosion patterns such as posterior glenoid wear in osteoarthritics will develop subluxation early on. Therefore implantation of any prosthesis is required to be done in the appropriate version as to avoid secondary instability through the prosthetic components. In the study undertaken here instability was found to be the most common complication in 44 shoulder revision surgeries. The result with an average Score of 41.9 recorded after Constant demonstrates that the excellent and good results obtained with primary arthroplasties can not be expected in revision surgery. Posterior instability may be present just as well as the more easily observed anterior instability. Separate to frank luxation or instability is the late cranialisation of the rotator cuff deficient shoulder which, although resulting in many cases in superior anterior subluxation, will mostly be seen as a late complication after arthroplasty.

Arthroplasty, Replacement↗
PubMed1999

Detrusor instability and low compliance may represent different levels of disturbance in peripheral feedback control of the micturition reflex.

BACKGROUND: Detrusor instability is a major cause of urinary incontinence in females. Its cause is unknown. Diagnosis is made with cystometry. A phasic pressure rise during cystometry diagnoses the unstable detrusor, and a non-phasic pressure rise the stable "low-compliance" detrusor. The aim was to test the hypothesis that such cystometric findings may represent different levels of disturbance in peripheral feedback control of a prematurely activated, but otherwise normal micturition reflex. Of 169 neurologically normal female incontinent patients (mean age, 50; mean parity, 3) urodynamically tested, 40 had detrusor instability and 16 had low compliance. Digital support of bladder base tested the peripheral control mechanism, and hand-washing the central control mechanism. The data were applied to a non-linear feedback equation with one variable, X(NEXT) = cX(1 - X), where c = central inhibition and X = fraction of possible nerve impulses in the micturition circuit. RESULTS: During filling, all 16 low-compliance patients had a bladder in the activated but stable closed state. Fourteen of the detrusor instability group could not suppress the micturition reflex and lost urine. During hand-washing, unexpectedly greater urine loss was noted in the low-compliance group (13 of 16) than in the detrusor instability group (24 of 40), chi2 (P < 0.005). With digital stretching, urge symptoms disappeared within a few seconds in 18/20 patients, and detrusor instability was suppressed in six patients. INTERPRETATION: The bladder has two stable states: open and closed. Closure is regulated by central and peripheral components. In the female, the peripheral component is controlled by the pelvic floor stretching the vagina to support the urine column. This prevents inappropriate activation of the micturition stretch receptors. In patients with low compliance, this peripheral control mechanism was sufficient to maintain the micturition reflex in an activated but stable closed state. In patients with detrusor instability, the micturition reflex could not be suppressed, swinging between the open and closed states. CONCLUSIONS: Demonstration of a peripheral musculoelastic control mechanism unlocks a new direction for management of female patients with non-neurological bladder instability. It is possible, using simple clinical methods based on digital vaginal stretching, to predict cure of instability by surgical tightening of the vagina and its supporting ligaments.

Adult↗
PubMed2001

Microsatellite instability in squamous cell carcinoma of head and neck from the Indian patient population.

Genomic instability in simple repeated sequences has been observed in several human cancers. We have analyzed 50 squamous cell carcinomas of the head and neck (SCCHN) and 5 pre-malignant severe dysplastic tissues from Indian patient populations for microsatellite instability in 18 different loci spread over eight different chromosomes. Among the tumors analyzed, 45% exhibited instability at two or more loci, and 15% exhibited instability at 40% of the markers tested. Similar analysis of SCCHN tumors from other populations (British, American and French) showed much less frequency of instability. SCCHN tumors in the present study did not show any instability in the mononucleotide repeat sequences. There is also a clear distinction in the nature of the instability in these tumors in comparison with colorectal tumors. These results suggest that the underlying mechanism generating this type of instability is different from those reported for colorectal tumors.

Adult↗
PubMed1983

Ventricular electrical instability: a predictor of death after myocardial infarction.

The results of a prospective study of ventricular electrical instability after myocardial infarction (MI) are presented. Ventricular electrical stability was assessed using a standardized protocol of programmed stimulation in 165 hemodynamically stable patients 6 to 28 days after acute MI. Ventricular electrical instability was defined as induction at programmed stimulation of ventricular fibrillation (VF) or ventricular tachycardia (VT) lasting at least 10 seconds. Of 165 MI survivors, 38 (23%) had ventricular electrical instability. No significant differences were noted between stable and unstable patients in terms of coronary prognostic index, elevation of serum creatine phosphokinase, coronary anatomy, site of MI, or frequency of VT within 48 hours of MI. The mean follow-up period was 8 months (range 0 to 12). There were 7 deaths in stable patients (5 from cardiogenic shock, 1 from septicemia, and 1 unwitnessed) and 10 deaths in unstable patients (8 instantaneous, 1 from cardiogenic shock, and 1 unwitnessed) during the subsequent year. In addition, 2 of 127 stable patients and 4 of 38 unstable patients had spontaneous VT from which they were satisfactorily resuscitated. Thus, the sensitivity of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 86% and the specificity 83%. The predictive accuracy of the absence of ventricular electrical instability as an indicator for the absence of instantaneous death or spontaneous VT was 98%. The predictive accuracy of the presence of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 32%. Thus, patients with ventricular electrical instability after MI have a high risk of instantaneous death within 1 year; patients without ventricular electrical instability after MI have a low risk of instantaneous death within 1 year; prospective studies of antiarrhythmic therapy and measures to prevent reinfarction and optimize left ventricular performance are required to determine whether instantaneous death can be prevented in unstable patients; and therapy to prevent reinfarction and optimize left ventricular performance may offer the best chance to improve prognosis in stable patients.

Adrenergic beta-Antagonists↗
PubMed2001

Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer.

Some studies have shown an inverse relationship between microsatellite instability in colon cancer and mutations in p53 and K-ras, whereas others have not. We therefore evaluated these features in a population-based sample of 496 individuals with colon cancer. Microsatellite instability was determined by a panel of 10 tetranucleotide repeats, the Bethesda consensus panel of mono- and dinucleotide repeats, and coding mononucleotide repeats in transforming growth factor-beta receptor type II, hMSH3, BAX, hMSH6, and insulin-like growth factor receptor type II. Mutations in codons 12 and 13 in K-ras were evaluated by sequencing. p53 overexpression (as detected by immunohistochemistry) was used as an indicator of p53 mutation; this was evaluated in 275 of the tumors. K-ras mutations were present in 33.2% of tumors, p53 overexpression in 51.5%, and microsatellite instability (as determined by the Bethesda consensus panel) in 12.5%. K-ras mutations were significantly less common in unstable tumors than stable tumors (11.8% versus 36.9%, P: < 0.001). p53 overexpression was significantly less common in unstable tumors than stable tumors (20.0% versus 55.7%, P: < 0.001). These inverse relationships between microsatellite instability and ras gene mutations and p53 overexpression were shown to be independent of tumor site in logistic regression analyses. All other measures of instability also showed statistically significant inverse relationships independent of tumor site with alterations in ras and p53, and instability results determined by the panel of 10 tetranucleotide repeats were highly significantly related to those determined by the Bethesda consensus panel. Coding mononucleotide repeat mutations were significantly more common in unstable tumors than stable tumors (85.7% versus 1.0%, P: < 0.001). We conclude that there is an inverse relationship between microsatellite instability and mutations in p53 and K-ras, and that the molecular profile of colon cancers with microsatellite instability is characterized by relatively infrequent mutations in K-ras and p53 and relatively frequent mutations in coding mononucleotide repeats.

Adult↗
PubMed2001

Detrusor instability in men: correlation of lower urinary tract symptoms with urodynamic findings.

PURPOSE: We evaluated the correlation of lower urinary tract symptoms suggestive of detrusor instability with urodynamic findings in men. MATERIALS AND METHODS: Enrolled in our prospective study were 160 consecutive neurologically intact men referred for urodynamic evaluation of persistent lower urinary tract symptoms. All patients had storage symptoms suggestive of detrusor instability. Patients were further clinically categorized according to the chief complaint of urge incontinence, frequency and urgency, nocturia or difficult voiding. The clinical and urodynamic diagnosis in all patients as well as specific urodynamic characteristics of those with detrusor instability were analyzed according to the these 4 clinical categories. RESULTS: Mean patient age was 61 +/- 15 years. The chief complaint was urge incontinence in 28 cases (17%), frequency and urgency in 57 (36%), nocturia in 30 (19%) and difficult voiding in 45 (28%). Detrusor instability was diagnosed in 68 cases (43%). A higher incidence of detrusor instability was associated with urge incontinence than with the other clinical categories (75% versus 36%, p <0.01). Of the patients 109 (68%) had bladder outlet obstruction, including 50 (46%) with concomitant detrusor instability. The prevalence of bladder outlet obstruction was similar in all patients regardless of the chief complaint. All other urodynamic diagnoses were also similar in the 4 clinical categories. The mean bladder volume at which involuntary detrusor contractions occurred were lower in patients with urge incontinence and frequency and urgency than in those with nocturia and difficult voiding (277.1 +/- 149.4 and 267.7 +/- 221.7 versus 346.7 +/- 204.6 and 306.2 +/- 192.1 ml., respectively, not statistically significant, p = 0.07). CONCLUSIONS: Detrusor instability and bladder outlet obstruction are common in men with lower urinary tract symptoms. The symptom of urge incontinence strongly correlated with detrusor instability. Other lower urinary tract symptoms did not correlate well with any urodynamic findings. Therefore, we believe that an accurate urodynamic diagnosis may enable focused and more efficient management of lower urinary tract symptoms in men.

Humans↗
PubMed2000

Dietary caffeine intake and the risk for detrusor instability: a case-control study.

OBJECTIVE: To determine whether there is an association in women between caffeine intake and risk for detrusor instability. METHODS: Women were included if they had symptoms of urinary incontinence, completed a 48-hour voiding diary detailing fluid and caffeine intake, and had undergone standardized multichannel urodynamics. The study group had 131 women with detrusor instability on provocative cystometry and maximum urethral closure pressure greater than 20 cm of water. The control group had 128 women without detrusor instability on provocative cystometry and maximum urethral closure pressure greater than 20 cm of water. For statistical comparison, women were divided into the following three groups on the basis of caffeine intake: minimal (< 100 mg/day), moderate (100-400 mg/day), and high (> 400 mg/day). RESULTS: The mean caffeine intake of women with detrusor instability (484 +/- 123 mg/day) was significantly higher than that of controls (194 +/- 84 mg/day, P =.002). On univariate analysis, significant risk factors for detrusor instability were age, smoking status, and caffeine intake. On multivariate analysis, the statistically significant association between high caffeine intake and detrusor instability persisted after controlling for age and smoking (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1, 6.5, P =.018). When women with moderate caffeine intake were compared with those with minimal caffeine intake, the risk for detrusor instability was lower and did not reach significant levels (OR 1.5, 95% CI 0.1, 7.2, P =.093). CONCLUSION: An association between high caffeine intake and detrusor instability was seen in this population. Larger studies are required to determine whether the association is causal.

Case-Control Studies↗
PubMed1999

Genetic disorders associated with cancer predisposition and genomic instability.

Genomic instability in its broadest sense is a feature of virtually all neoplastic cells. In addition to the mutations and/or gene amplifications that appear to be a prerequisite for the acquisition of a neoplastic phenotype, human cancers exhibit other "markers" of genomic instability--in particular, a high degree of aneuploidy. Indeed, many studies have shown that aneuploidy is an almost invariant feature of cancer cells, and it has been argued by some that the emergence of aneuploid cells is a necessary step during tumorigenesis. The functional link between genomic instability and cancer is strengthened by the existence of several "genetic instability" disorders of humans that are associated with a moderate to severe increase in the incidence of cancers. These disorders include ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, xeroderma pigmentosum, and Nijmegen breakage syndrome, all of which are very rare and are inherited in a recessive manner. Analysis of the cells from such cancer-prone individuals is clearly a potentially fruitful approach for delineating the genetic basis for instability in the genome. It is assumed that by identifying the underlying cause of genetic instability in these disorders, one can derive valuable information not only about the basis of particular genetic diseases, but also about the underlying causes of genomic instability in sporadic cancers in the general population. In this article, we review the clinical and cellular properties of genetic instability disorders associated with cancer predisposition. In particular, we focus on the rapid advances made in our understanding of these disorders that have derived from the cloning of the genes mutated in each case. Because in many instances the affected genes have analogs in lower eukaryotic species, we shall discuss how studies in yeasts in particular have proved valuable in our understanding of human diseases and predisposition to cancer.

Animals↗
PubMed1998

Mononucleotide repeat instability is infrequent in neuroblastoma.

Neuroblastoma is a pediatric malignancy of the sympathetic nervous system and is frequently characterized by genetic aberrations (including aneuploidy, chromosomal deletions, translocations, and gene amplification) that suggest inherent genomic instability. Mutations in mismatch repair (MMR) genes have been associated with genomic instability in several human cancers, such as those of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. In these cases, replication errors at microsatellite repeats lead to microsatellite instability (MSI) and mutagenesis. In neuroblastoma, we and others have detected MSI infrequently when analyzed at di- or tetranucleotide repeat polymorphic markers. More recently, however, mutations in the MMR gene GTBP/hMSH6 have been associated with a limited phenotype of instability at mononucleotide repeats only (e.g., polyadenine tracts). Furthermore, mononucleotide repeats appear to be common downstream targets of MSI-related mutagenesis and are present in the transforming growth factor-beta receptor-II gene (TGF beta RII), the BAX proapoptosis gene, and the insulin-like growth factor II receptor gene (IGFIIR) frequently in tumors arising in HNPCC kindreds. Therefore, we analyzed 46 matched normal and tumor DNAs representing all clinical stages of neuroblastoma with the use of five polymorphic mononucleotide repeat markers to assess for MSI at mononucleotide repeats. Only one tumor (2%) demonstrated mononucleotide repeat instability, and the instability was at a single locus. We conclude that MSI, including mononucleotide repeat instability, is infrequent in human neuroblastoma, and therefore defects in DNA mismatch repair are not responsible for the genomic instability seen in this neoplasm.

Autoradiography↗
PubMed1998

Genetic instability of microsatellite sequences in non-small cell lung cancers.

To evaluate the frequency and pattern of microsatellite instability in NSCLCs, we examined 36 cases of resected NSCLC. The mean age of the patients was 59.9+/-8.4 years. There were 19 cases of squamous cell carcinoma, 15 of adenocarcinoma and two of large cell carcinoma. We observed microsatellite instability at one or more loci in 13 (36%) of 36 tumors analyzed, and this instability ranged from six tumors showing instability in only a single microsatellite to three tumors that had alterations in three of four tested microsatellites. The microsatellite that showed instability most frequently in these tumors was D3S1340 (31%). Microsatellite instability was found in five (26%) of 19 squamous cell carcinomas, six (40%) of 15 adenocarcinomas, and in both large cell carcinomas tested. We found microsatellite instability in four (24%) of 17 cancers at stage I, in one (17%) of six at stage II, in eight (73%) of eleven at stage IIIa, and in neither at stage IIIb. In conclusion, microsatellite instability was noted in at least one third of non-small cell lung cancers, suggesting its possible role in cancer development.

Adenocarcinoma↗