Behavioural phenotype of SYNGAP1-related intellectual disability.

BACKGROUND: SYNGAP1- related intellectual disability (SYNGAP1-ID) is a rare genetic disorder presenting with intellectual disability (ID), epilepsy, maladaptive behaviours and communication challenges. To date, few studies have assessed the context in which these maladaptive behaviours occur. This study aims to investigate the prevalence of problem behaviours, characterise the behavioural phenotype and use well-validated measures to explore variables that maintain the behaviours. METHODS: Our sample includes 19 individuals diagnosed with SYNGAP1-ID and their parents. Parents provided information on behaviours that their children engage in, as well as their general behavioural dispositions. Well-validated measures (e.g., the Repetitive Behaviour Scale-Revised, Sensory Profile-2 and Vineland Adaptive Behaviour Scale) were used. A subset of individuals underwent further direct experimental assessment of their problem behaviour to identify the variables maintaining those problem behaviours. Parental reports were analysed using nonparametric statistical analysis; the direct assessments of individuals' problem behaviour were analysed using visual analysis and validated supplemental measures. RESULTS: All 19 individuals engaged in some form of maladaptive problem behaviour. Ratings of ritualistic, sameness and restricted behaviours measured by the RBS-R were commensurate with individuals diagnosed with idiopathic autism spectrum disorder (ASD) while self-injurious behaviours were endorsed at a higher level in SYNGAP1-ID when compared with idiopathic ASD. The problem behaviours in our cohort of patients with SYNGAP1-ID were maintained by automatic reinforcement and social attention and are positively correlated with atypical sensory responses. CONCLUSIONS: Individuals with SYNGAP1-ID engage in problem behaviours commensurate with other populations (e.g., those with ASD), they exhibit atypical response to sensory stimuli. Problem behaviours were frequently maintained by automatic reinforcement, which may result from a dysregulated sensory system. Children with SYNGAP1-ID may benefit from strategies used in persons with ASD.

Classification of injuries observed in functional classes of self-injurious behaviour.

BACKGROUND: Limited research has examined how the functions of self-injurious behaviour (SIB) relate to the production of injuries and the location, type or severity of those injuries. METHODS: Clinical and medical records were coded for 64 individuals hospitalised for SIB. When injuries were present, the physical properties of SIB and injuries were assessed across groups of individuals with automatically and socially maintained SIB. RESULTS: Injuries were observed for 35 of the individuals who engaged in SIB. Individuals who engaged in a single form of SIB were more likely to have injuries (P < .05). Individuals with SIB maintained by automatic reinforcement had significantly more severe injuries to the head than those in the social group (q < .05, P = .0132, H = 12.54). CONCLUSION: Although results are preliminary, the results provide evidence that the function of SIB may influence the severity and location of injuries produced.

Predicting the patient at low risk for lymph node metastasis with localized prostate cancer: an analysis of four statistical models.

PURPOSE: Statistical models using preoperative Prostate-Specific Antigen, Gleason primary grade or score of the biopsy specimen, and clinical stage have been developed to predict those patients with clinically localized prostate cancer at low risk for lymph node metastasis. It has been recommended that these patients do not require pelvic lymph node dissections. Four such models were evaluated to assess their accuracy in identifying this subgroup of patients. METHODS AND MATERIALS: We reviewed the records of 214 patients with clinically localized prostate cancer who underwent pelvic lymph node dissections. Data from these patients were entered into the four models. RESULTS: Lymph node metastasis was detected in 14% of patients. The results showed the following for each of the proposed models respectively: 78, 50, 76, and 42% of the patients were identified as low risk and, hence, would be spared pelvic lymph node dissections. The false negative rates are 13 (7.8%), 5 (4.6%), 14 (8.6%), and 1 (1.1%). Sensitivities are 56.7, 83.3, 53.3, and 96.7%. CONCLUSIONS: While the pelvic lymph node dissection is the most accurate method of detecting occult nodal metastasis, statistical models can identify a cohort of low risk patients that may be spared lymphadenectomy.

Cryosurgical ablation of the prostate: two-year prostate-specific antigen and biopsy results.

OBJECTIVES: Percutaneous cryosurgical ablation of the prostate (CSAP) was performed on patients with localized or locally advanced adenocarcinoma of the prostate. To assess local disease control, post-treatment biopsy and serum prostate-specific antigen (PSA) levels were obtained at 3 and 24 months post-treatment. METHODS: From June 1990 through May 1994, CSAP was performed 448 times on 383 patients under Institutional Review Board protocols. A urethral warming catheter was used for all procedures. A total of 239 patients were followed for a minimum of 21 months after treatment. None of this group had received prior local treatment. The group consisted of patients who were newly diagnosed and treated solely with cryotherapy (virgin); the remainder had been on androgen deprivation therapy (ADT) prior to CSAP. RESULTS: Biopsies were obtained from 114 patients at 21 months or more after treatment. In the virgin group, 79% had a negative biopsy after one or more treatments, and 88% of the ADT group are negative after one or more treatments. Overall, 69% had a negative biopsy after one treatment and 82% had a negative biopsy following one or more CSAP treatments. Of a group of 163 patients, PSA data were evaluable at 21 months or more after treatment. In the virgin group, 60% had a PSA 0.4 ng/mL or less, and 77% had a PSA 1.0 ng/mL or less. In the ADT group, 40% had a PSA 0.4 ng/mL or less, and 69% had a PSA value of 1.0 ng/m Lor less. Complications were minimal, the most common one being urethral tissue sloughing, which occurred in 10% of patients. CONCLUSIONS: CSAP appears to be effective in obtaining local control as measured by biopsy and PSA 21 months or more post-treatment. When retrospectively comparing our results with recently published radiotherapy series, CSAP was more effective in obtaining nadir PSA values 1.0 ng/mL or less and negative biopsies at 21 months or more after treatment.

The role of the periosteum in the growth of long bones. An experimental study in the rabbit.

Hemicircumferential division of the periosteum was performed on the upper tibia of the rabbit. Division of the medial side regularly caused a valgus angulation, but other injuries about the upper tibia had no effect. The cause of deformity after periosteal damage is discussed.

Kienböck's disease in cerebral palsy.

Five cases of Kienböck's disease occurring in a group of fifty-three adults with cerebral palsy are described. The increased incidence of the disease is attributed to the flexed posture habitual in the affected wrist and to an effect on the pattern of blood supply to the lunate.

Metal sensitivity in patients undergoing hip replacement. A prospective study.

A prospective study of allergic contact dermatitis after metal-on-plastic total hip replacement was undertaken in 69 patients, of whom 54 were available for review after operation. Before operation six patients were metal sensitive, but only one remained so afterwards; this patient had given a clear history of metal sensitivity and a titanium prosthesis had therefore been used. In all six patients the result of the operation was good and no case of loosening occurred. Sixty-three patients had negative patch tests before operation; in none of these was metal sensitivity detected after operation. Cutaneous sensitivity to various metals is well documented after the insertion of metal-on-metal prostheses and in failed prostheses. We have not found any such increased sensitivity after metal-on-plastic hip replacement. There is little evidence of a direct causal relationship between metal sensitivity and subsequent loosening. The cutaneous sensitivity may be the consequence of loosening rather than its cause. Our results suggest that, providing metal-on-plastic prostheses are used, routine patch testing before hip replacement is no longer required.

A prospective, randomised study to compare extracorporeal shock-wave therapy and injection of steroid for the treatment of tennis elbow.

We undertook a prospective, randomised study to compare the analgesic effect of injection of steroid and of extracorporeal shock-wave therapy (ESWT) for the treatment of tennis elbow. Group 1 received a single injection of 20 mg of triamcinolone with lignocaine while group 2 received 2000 shock waves in three sessions at weekly intervals. After six weeks there was a significant difference between the groups with the mean pain score for the injection group falling from 66 to 21 compared with a decrease from 61 to 35 in the shock-wave group (p = 0.05). After three months, 84% of patients in group 1 were considered to have had successful treatment compared with 60% in group 2. In the medium term local injection of steroid is more successful and 100 times less expensive than ESWT in the treatment of tennis elbow.

The embryological congruity of the human hip joint.

The embryology of the hip joint has been studied in a series of 32 embryos. The formation of the skeletal elements together with the capsule, glenoid, acetabular ligament, and ligamentum teres is followed until the definitive form is present. The congruity of the hip joint is established as soon as the joint cavity is formed.

Spontaneous rupture of the anterior cruciate ligament after anabolic steroids.

Anabolic steroids remain popular among body builders and power athletes despite numerous warning about their side effects. A case of spontaneous rupture of the anterior cruciate ligament is reported in a bodybuilder taking steroids. While there are many published reports of tendon rupture associated with steroid intake, the authors could find no report relating to ligament disruption.

Single-dose cephalexin therapy for acute bacterial urinary tract infections and acute urethral syndrome with bladder bacteriuria.

The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected populations of women of a wide age range treated for acute uncomplicated urinary tract infections with a single dose of amoxicillin or trimethoprim-sulfamethoxazole (J. Rosenstock, L. P. Smith, M. Gurney, K. Lee, W. G. Weinberg, J. N. Longfield, W. B. Tauber, and W. W. Karney, Antimicrob. Agents Chemother. 27:652-654, 1985; N. E. Tolkoff-Rubin, M. E. Wilson, P. Zuromskis, I. Jacoby, A. R. Martin, and R. H. Rubin, Antimicrob. Agents Chemother. 25:626-629, 1984). The cure rates of (87%) for our younger patients, those less than 25 years of age, was better than that (46%) for our patients over 40 years of age (P less than 0.001). Patients with infections that were negative in an antibody-coated bacteria test were cured at a significantly higher rate than those with infections that were positive in an antibody-coated bacteria test (71 versus 19%; P = 0.003). Those patients with infections caused by cephalexin-susceptible organisms were cured at a rate similar to that for patients with infections caused by cephalexin-resistant organisms (68 versus 50%; P = 0.62). The cure rate for suburban patients was 90%, versus 45% for inner-city patients (P = 0.008). Of the 28 women with acute urethral syndrome due to low-level bacteriuria, 27 were cured.

Biochemical identification of elastin in periosteum and pericranium.

Histologic observations of elastic in periosteum have never been confirmed biochemically. Elastins were isolated, quantitated and characterized from human periosteal and pericranial tissues. Periosteum contains approximately 2.1% elastin by weight and does not appear to vary between skeletally mature and immature donors. Pericranium contains approximately 2.7% elastin by weight. These elastin contents are comparable to that reported for human skin. Amino acid analyses of the elastin from periosteum and pericranium showed the characteristic, non-polar amino acid composition of elastin. Proportions of the polar amino acids were somewhat elevated compared with elastins from the ligamentum and the aorta but were similar to those isolated from cartilaginous sources. The desmosine contents of the periosteal and pericranial elastins were comparable to those of elastins from other sources.

Histological presence of viable prostatic glands on routine biopsy following cryosurgical ablation of the prostate.

PURPOSE: Cryosurgical ablation of the prostate has recently received much attention as a therapeutic alternative for the treatment of localized prostatic adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes as well as unaltered prostatic glandular epithelial elements. Prostate specific antigen (PSA) remains undetectable in the majority of men. However, in some PSA increases without demonstrable local recurrence. MATERIALS AND METHODS: A total of 383 patients underwent 447 procedures between June 1990 and January 1994. Of 358 biopsies performed at our institution, 317 (2,075 cores) were available for review. Each core was examined for unaltered prostatic glandular epithelial elements and then scored for the percentage of epithelial glandular involvement according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50 to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements. RESULTS: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10% and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were positive for residual carcinoma. Among 55 cases with more normal epithelium per core 24 (43.6%) were positive for residual carcinoma. Patients with a positive biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124). CONCLUSIONS: Cryosurgical ablation of the prostate has the ability to ablate prostatic tissue completely, thus rendering it free of glandular elements as determined by biopsy. Increasing PSA can indicate residual glandular elements. Increases in unaltered prostatic glandular epithelial elements with time are not paralleled by increased rates of local disease recurrence. undetectable serum PSA has a low risk of residual unaltered prostatic glandular epithelial elements and localized carcinoma. Results as measured by unaltered prostatic glandular epithelial elements and PSA improve with the surgical experience.

Biomarkers in monitoring for efficacy of immunotherapy and chemoprevention of bladder cancer with dimethylsulfoxide.

This study correlated biomarkers expressed in tumor and epithelial field with clinical response and recurrence. Of 25 bladder cancer patients, 11 received 6 weeks of intravesical Bacille Calmette-Guerin (BCG), and 14 were treated weekly with intravesical dimethylsulfoxide (DMSO) for 4 weeks to further modulate biomarker expression. G-actin, DNA aneuploidy, and p300 tumor antigen were evaluated by quantitative fluorescence image analysis on uroepithelial cells from bladder wash samples prior to and immediately following treatment. Excluding patients who did not respond to BCG (and who had persistently abnormal p300 and DNA markers), recurrence correlated with persistent abnormal G-actin findings. Of patients who were G-actin negative following therapy, only 25% recurred during follow-up in contrast to 67% in patients who were positive (p < 0.03 by Fisher's exact test). The odds ratio for recurrence was 6.00 (95% confidence interval: 1.3-28.6). Cytosolic G-actin levels can be an important intermediate end point marker for chemoprevention.

Salvage radiotherapy for prostate cancer recurrence after cryosurgical ablation.

OBJECTIVES: To retrospectively determine the outcome of patients treated with salvage three-dimensional conformal radiotherapy (RT) for prostate cancer recurrence after cryosurgical ablation of the prostate (CSAP). Biochemical control rates and morbidity were analyzed. METHODS: Between January 1990 and November 1999, a total of 49 patients initially treated with CSAP were later irradiated because of a rising prostate-specific antigen (PSA) level and/or a positive biopsy at Allegheny General Hospital. The clinical stage before cryosurgery was T1c in 7 patients; T2a in 7 patients; T2b in 10 patients; T3 in 17 patients; and T4 and/or N1 in 8 patients. The Gleason score was 6 or lower in 29 patients, 7 in 11 patients, and 8 or higher in 9 patients. The mean pre-CSAP PSA level was 15.7 ng/mL (range 2.4 to 45). One patient had a PSA level less than 4 ng/mL, 16 had a PSA level of 4 to 10 ng/mL, 21 had a PSA level of 10 to 20 ng/mL, and 11 had a PSA level greater than 20 ng/mL. Before the start of RT, a complete restaging workup was performed and was negative for distant metastatic disease in all 49 patients. The mean interval to recurrence after CSAP was 19 months (range 3 to 78). The mean RT dose to the planning target volume was 62.9 Gy (range 50.4 to 68.4). RESULTS: The mean pre-RT PSA level was 2.4 ng/mL (range 0.1 to 7.4). After RT, the mean nadir PSA level was 0.4 ng/mL (range 0 to 4.2). The mean time to PSA nadir was 5.8 months (range 1 to 15). In 42 patients, the PSA nadir was less than 1.0 ng/mL, in 5 patients the PSA nadir was greater than 1 ng/mL, and in 2 patients the PSA level remained stable. With a median follow-up time of 32 months (range 12 to 85), the overall biochemical control rate was 61%. The mean time to biochemical failure was 14.5 months (range 1 to 47). Of 30 patients with a pre-RT PSA level of 2.5 ng/mL or less, the disease of 22 (73%) was controlled compared with only 8 (42%) of 19 with a pre-RT PSA level greater than 2.5 ng/mL (P = 0.040). Biochemical control occurred in 18 (69%) of 26 patients with a dose of 64 Gy or greater compared with only 12 (52%) of 23 patients with a dose of less than 64 Gy (P = 0.024). The disease of 20 (70%) of 29 patients with a Gleason score of 6 or lower was controlled versus 10 (50%) of 20 patients with a Gleason score of 7 or greater (P = 0.064). Only 2 patients developed subacute morbidity (proctitis and a urethral stricture). All complications resolved with conservative measures. CONCLUSIONS: Salvage RT for prostate cancer recurrence after CSAP appears feasible. Our preliminary experience revealed that post-CSAP RT in patients with prostate cancer appears to effectively diminish the post-RT PSA level to a nadir of 1.0 ng/mL or less in most patients. The pre-RT PSA level and radiation dose may be important predictors of biochemical control in the salvage setting. RT as described was associated with minimal toxicity to the gastrointestinal/genitourinary systems. Additional prospective randomized studies are necessary to better assess the role of RT in the treatment of these patients.