Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders.

Alterations in glutamatergic transmission onto developing GABAergic systems, in particular onto parvalbumin-positive (Pv(+)) fast-spiking interneurons, have been proposed as underlying causes of several neurodevelopmental disorders, including schizophrenia and autism. Excitatory glutamatergic transmission, through ionotropic and metabotropic glutamate receptors, is necessary for the correct postnatal development of the Pv(+) GABAergic network. We generated mutant mice in which the metabotropic glutamate receptor 5 (mGluR5) was specifically ablated from Pv(+) interneurons postnatally, and investigated the consequences of such a manipulation at the cellular, network and systems levels. Deletion of mGluR5 from Pv(+) interneurons resulted in reduced numbers of Pv(+) neurons and decreased inhibitory currents, as well as alterations in event-related potentials and brain oscillatory activity. These cellular and sensory changes translated into domain-specific memory deficits and increased compulsive-like behaviors, abnormal sensorimotor gating and altered responsiveness to stimulant agents. Our findings suggest a fundamental role for mGluR5 in the development of Pv(+) neurons and show that alterations in this system can produce broad-spectrum alterations in brain network activity and behavior that are relevant to neurodevelopmental disorders.

Beamforming approach to phase-amplitude modulation analysis of multi-channel EEG.

Phase-amplitude modulation is a form of cross frequency coupling where the phase of one frequency influences the amplitude of another higher frequency. It has been observed in neurophysiological recordings during sensory, motor, and cognitive tasks, as well as during general anesthesia. In this paper, we describe a novel beamforming procedure to improve estimation of phase-amplitude modulation. We apply this method to 64-channel EEG data recorded during propofol general anesthesia. The method improves the sensitivity of phase-amplitude analyses, and can be applied to a variety of multi-channel neuroscience data where phase-amplitude modulation is present.

Increased incidence of diabetes mellitus in the patients with transitional cell carcinoma of urinary bladder.

The progression of bladder cancer to invasive disease is highly dependent on its ability to penetrate basement membrane of urothelium. Studies on diabetic nephropathy have shown a reduction in proteoglycan content of the glomerular basement membrane. Based on the well-known fact that proteoglycans are one of the main components of basement membrane and extracellular matrix we assessed the relationship between diabetes mellitus, bladder cancer incidence and its behavior. These studies include 252 patients with microscopically confirmed transitional cell carcinoma of bladder, and 549 patients with other urological disorders who served as controls. The prevalence of diabetes mellitus in each group was assessed. The group of patients suffering from transitional cell carcinoma was divided according to etiological risk factors such as cigarette smoking, diabetes and patients that were non-smokers and did not suffer from diabetes mellitus. We assessed the features of bladder cancer behavior in each group. Logistic regression model estimation for statistical analysis was used, with transitional cell carcinoma as a dependent binary variable and age, sexes smoking and diabetes as independent variables. Statistical significance was considered at two levels: p

Metachronous renal cell carcinoma metastasis to the contralateral adrenal gland.

OBJECTIVES: Metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland is very rare. We review our experience with 5 such patients and compare it with reports in the literature. METHODS: The records of all 350 patients who underwent nephrectomy for renal cell carcinoma in our center between 1975 and 1992 were reviewed. Five patients were found to have had solitary metachronous metastases to the contralateral adrenal gland on follow-up. RESULTS: The adrenal metastasis was discovered 18 to 210 months (mean 66.8) after nephrectomy. In 2 patients the lesion was found incidentally on routine computed tomography scan; in the other 3 patients, diagnosis was by ultrasonography, performed because of flank pain and weight loss or routine follow-up. All patients underwent adrenalectomy. Survival ranged from 8 to 64 months (mean 36.4); 3 patients had no evidence of disease at 42, 44, and 64 months postoperatively, and 2 patients died of pulmonary metastasis at 8 and 24 months. Analysis of the clinical data of our 5 patients together with the 9 we found in the published reports revealed that the mean interval between nephrectomy and the appearance of adrenal metastasis was shorter in the patients who died. CONCLUSIONS: The results of adrenalectomy for metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland are unpredictable. The prognosis is somewhat better when the mean interval between the nephrectomy and the appearance of the adrenal metastasis is longer than 18 months. We recommend adrenalectomy because long-term survival is expected in some of these patients.

Increased rate of nondisjunction in sex cells derived from low-quality semen.

The relationship between chromosomal nondisjunction and semen quality was studied in two groups of males who differ highly in their semen quality: 12 individuals with low-quality semen caused by varicocele, and 8 subjects with high-quality semen, selected from sperm donors for in vitro fertilization. Chromosomal nondisjunction was inferred from the rate of disomy found in mature sperm cells. To determine the rate of disomy, we applied fluorescence in situ hybridization using satellite-specific probes for chromosomes 1, 15, 18, X and Y. In sperm cells of males with low-quality semen, the mean rate of disomy for each of the autosomes and of hetero-disomy for the sex chromosomes (XY) was significantly higher than that observed in the high-quality semen samples: more than 15-fold higher for chromosomes 1 and 15, and 7-fold higher for chromosomes 18 and XY. Yet, the homo-disomy rate for each of the sex chromosomes (XX and YY) was almost the same in both types of semen. The large discrepancy between the low- and high-quality semen in the rate of sex chromosome hetero-disomy versus the similar rate of homo-disomy strongly suggests that the abnormal chromosomal segregation in meiocytes of males with low-quality semen resulted from chromosomal nondisjunction at the first meiotic division. The results indicate that men showing poor semen quality are at an increased risk for meiotic nondisjunction, similar to women at the end of their reproductive years.

Human prostatic tissue constituents respond differently to thermal injury induced by Nd-YAG laser ITT fiber applied ex-situ.

BACKGROUND AND OBJECTIVE: The human prostate is a glandular organ that has intervening fibromuscular elements. The objective of this study was to evaluate the thermocoagulative effect on the different components of the organ exposed to Nd-YAG laser irradiation using a new ITT optic fiber design (Interstitial Thermal Therapy). STUDY DESIGN/PATIENTS AND METHODS: Twelve fresh transvesical prostatectomy specimens were irradiated ex-situ at 4 to 6 sites using an ITT fiber with laser energies ranging from 900 to 4500 joules (J) applied at times ranging from 60 to 300 seconds corresponding to 10 to 15 watts. The specimens were serially sectioned to include the proximal, mid and distal regions of the centrally coagulated channel. An ocular grid was utilized to measure the radius (r) of thermal injury from the margin of the centrally coagulated channel to the furthermost detectable area of thermally induced changes. RESULTS: The maximal extent of thermal injury was seen at the mid-length of the irradiated channel at energy of 2700 J (15w/180 sec). The fibromuscular compartment of the prostate was more affected (r = 855 microm) and showed more interstitial vacuolization and charring than the adenomatous one (r = 495 microm). Utilization of higher energy doses did not significantly alter the depth of injury but did reduce the extent of interstitial vacuolization of both components. CONCLUSION: The study indicates that the extent of laser induced coagulative necrosis depends on the histologic architecture of the prostate and also varies in extent along the length of the channel surrounding the fiber.

Transvesical prostatectomy in elderly patients.

PURPOSE: We assessed the results of transvesical prostatectomy in patients older than 80 years. MATERIALS AND METHODS: We studied 98 patients 80 to 90 years old who underwent transvesical prostatectomy between 1986 and 1993, including those with a large prostate (preoperative estimated weight more than 80 gm.), numerous or large cystolithiasis and large bladder diverticulum, which are indications for open prostatectomy. Clinical data were obtained by chart review. RESULTS: The indications for surgery were urinary retention in 53 patients (54%), severe obstructive urinary symptoms in 18 (18.4%), cystolithiasis in 17 (17.3%), prostatic bleeding in 10 (10.2%) and bladder diverticulum in 2 (2%). Accompanying diseases were present in 69 patients (70.6%), including ischemic heart disease in 41 (42%), diabetes mellitus in 17 (17.3%) and arterial hypertension in 14 (14.3%). A total of 59 patients (60.2%) underwent surgery while under general anesthesia and 39 (39.8%) received regional anesthesia. Average operative time was 62 minutes. Of the patients 40 (40.8%) received 1, 14 (14.3%) received 2 and 2 (2%) received 4 units of blood. No postoperative deaths or life threatening complications were noted. The immediate postoperative complications included urinary tract infection in 20 patients (20.5%), wound infection in 3 (3.0%) and orchiepididymitis in 3 (3.0%). Postoperative mild to moderate incontinence was noted in 2 patients (2.0%). Bladder neck constriction and urethral strictures occurred in 4 (4.1%) and 3 (3.0%) patients, respectively. CONCLUSIONS: Transvesical prostatectomy can be performed safely in elderly patients with a low morbidity rate.

The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases.

OBJECTIVE: To describe the clinical course and histological features of transitional cell carcinoma (TCC) of the bladder with microcysts. PATIENTS AND METHODS: Among 940 patients with bladder TCC diagnosed at our institution during a 5 year period. 12 (1.2%; eight men and four women, mean age 71.1 years, range 52-85) were diagnosed histologically as having microcystic TCC. Sections of the tumours were stained with haematoxylin and eosin, periodic acid-Schiff and Alcian blue and clinical data obtained from the patients' records. RESULTS: Of the 12 patients with bladder TCC with microcysts, three had tumours confined to the epithelium, six had tumour invasion of the lamina propria and three had muscle invasion. One patient had low-grade TCC and 11 had high-grade TCC; six patients had a second primary tumour; three had a colon carcinoma, one a villous adenoma of the caecum, one a locally advanced carcinoma of the prostate and the last a squamous cell carcinoma of the uterine cervix. CONCLUSIONS: Microcystic TCC was associated with high-stage and high-grade bladder tumours and with other primary tumours, especially of the colon. Screening these patients for asymptomatic tumours of the colon is suggested.

The role of external sphincterotomy for patients with a spinal cord lesion.

For the last three decades external sphincterotomy has been well accepted as a treatment for bladder outlet obstruction in patients with a spinal cord lesions. Recently, however, its value has been brought into question. To assess the current place of this procedure in the treatment of the neuropathic bladder of spinal origin, we studied the outcomes of sphincterotomy in 32 patients. Post-voiding residual urine volume decreased after surgery in 27 patients (84%), considerably in 22 (69%) of them. Clinical infection resolved in 14 out of 19 patients (74%), hydronephrosis disappeared in two out of three (66%), and vesicourethral reflux improved in three out of five (60%) and was cured in two (40%). Six of the patients (19%) were freed from catheterization, but two patients (6%) lost partial continence. Sphincterotomy is an important tool in the treatment of spinal patients with bladder outlet obstruction and should be considered when the proper indications exist.

[Anterior vaginal wall and pelvic floor sling for stress incontinence].

There is considerable doubt as to whether the intra-abdominal position of the urethra is the critical factor in maintenance of continence. Recent studies have suggested that a firm, supportive, suburethral layer is required for urethral closure during effort. The surgical procedure we describe is performed by vaginal approach and involves creation of a sling from the vaginal wall and underlying musculofascial layer, that provides compression and support for the urethra and resuspends the bladder neck. 20 women (37-70 years, mean 48.4) with severe stress incontinence (average of 5 wet pads per day) underwent the sling procedure between October 1994 and July 1995. 10/20 had had previous pelvic surgery (6 anti-incontinence procedures and 4 hysterectomies). 3/20 had intrinsic sphincter dysfunction and the rest a hypermobile urethra. The surgical technique was easily performed. Postoperative complications were minimal, and included blood transfusion in 3 and in 5 suprapubic pain which subsided spontaneously or after oral diclofenac. The cystostomy was closed after 10.5 days (range 3-49) when voiding resumed and urine residual became less than 60 ml. The median follow-up was 9.4 months (range 3-12). All patients were cured and satisfied. 2/20 reported onset of urge incontinence which was found urodynamically to be de-novo detrusor instability due to urethral obstruction. On the other hand, all 3 patients with associated urge incontinence reported its disappearance postoperatively. These results are encouraging and this surgical procedure seems to provide a good solution for all types and grades of stress incontinence. Long-term follow-up is required to determine persistence of the good results.

The pattern of radionuclide scrotal scan in torsion of testicular appendages.

The aim of this study was to define the radionuclide scrotal imaging (RSI) pattern in cases of torsion of testicular appendages and to correlate it with the duration of symptoms. Two hundred and seventeen patients with acute scrotal pain were evaluated prospectively during the past 13 years. Two groups of patients were defined according to the interval between the onset of symptoms and the performance of RSI: group A comprised patients in whom RSI was performed within 5 h after the onset of symptoms, while group B comprised patients in whom RSI was performed between 5 and 24 h after the onset of symptoms. An SPX-4 Elscint or an Apex 405 gamma camera with a parallel hole or converging collimator was used. Between 5 and 15 mCi of technetium-99m pertechnetate was injected as a bolus intravenously. The radionuclide angiogram consisted of six to eight consecutive 5-s frames. The scrotal static scan was obtained immediately following the radionuclide angiogram. The "hot dot" sign, which is a small spot of increased tracer perfusion and uptake on RSI, was not present during the first hours after the onset of symptoms. Therefore, RSI is inaccurate and is not indicated for the diagnosis of torsion of testicular appendages of less than 4-5 h duration. The hot dot sign was, however, demonstrated on the RSI in 45% of the patients with scrotal pain lasting between 5 and 24 h. The overall sensitivity and accuracy of RSI in diagnosing torsion of testicular appendages in this group of patients were 68% and 79%, respectively. In all the patients with a positive hot dot sign, torsion of testicular appendages was found at exploration (specificity 100%). Therefore, the hot dot sign was found to be pathognomonic of torsion of testicular appendages.

Evaluation of mucinous metaplasia of the prostate gland by mucin histochemistry.

OBJECTIVE: To evaluate the presence of mucinous metaplasia in normal and benign hyperplastic prostates, using stains for neutral and acidic mucins. PATIENTS, MATERIALS AND METHODS: Normal prostate glands were removed during the post-mortem examination of 11 consecutive subjects (median age 45 years, range 17-79) who had died accidentally. Specimens were also obtained from 10 patients (median age 70.2, range 61-82) undergoing suprapubic prostatectomy for prostatic hyperplasia. The specimens were examined histologically; sections were stained using the periodic acid-Schiff (PAS) method for neutral mucins and the alcian blue (AB) method at pH 2.5 for acidic mucins. The positive sections were also immunostained for high molecular weight cytokeratin (KER), and prostate-specific antigen (PSA) using the strept-avidin-biotin (SAB) method. RESULTS: Mucinous metaplasia was found in six of the normal prostates and in three of the hyperplastic glands. Usually, the cells were tall columnar, containing both AB- and PAS-positive material. The cells were negative both for PSA and KER. Mucinous metaplasia affected all ages, including a 17-year-old, and mostly involved the inferior periurethral area. CONCLUSION: Benign mucinous metaplasia was more frequent than previously appreciated, involved all ages, was mainly periurethral and did not correlate with the usual distribution of adenocarcinoma of the prostate.

The value of radionuclide scrotal imaging in the diagnosis of acute testicular torsion.

OBJECTIVE: To assess the accuracy of radionuclide scrotal imaging (RSI) in the diagnosis of testicular torsion and torsion of testicular appendages. PATIENTS AND METHODS: Eighty-seven patients (mean age 30.1 years, range 8-65) who presented with acute scrotal pain were evaluated by RSI and the results correlated with the clinical and surgical findings. RESULTS: Of the 87 patients, 44 underwent scrotal exploration and 42 patients were treated conservatively. One patient with a 'missed torsion' pattern on RSI refused operation and was lost to follow-up. Of the 44 patients who underwent surgery, testicular torsion was found in 30 and torsion of testicular appendages in 14 patients. The specificity of the RSI in diagnosing testicular torsion was 100% and the sensitivity was 98%. An area of increased tracer activity in the presence of a normal radionuclide angiogram was suggestive of torsion of testicular appendages with a specificity of 93%. Of the 42 patients who were treated conservatively, 19 had epididymitis, according to clinical and RSI findings, 10 had torsion of testicular appendages, two had orchiepididymitis, two had hydrocele, two had haematocele and seven patients had normal testes. At a follow-up examination, normal testicles were found in all 42 patients. CONCLUSION: The RSI may assist in the evaluation of nontraumatic acute scrotum, and can clearly distinguish among testicular torsion, torsion of testicular appendages and epididymitis.

Changing trends in the management of iatrogenic ureteral injuries.

PURPOSE: We evaluated changing trends in the management of late diagnosed iatrogenic ureteral injuries before and after the introduction of percutaneous nephrostomy. MATERIALS AND METHODS: The study included 44 patients of whom 24 were treated primarily by immediate reconstructive surgery from 1979 to 1984 and 20 were treated primarily by percutaneous nephrostomy tube insertion beginning in 1985. RESULTS: Six of the 24 patients underwent ureteroneocystostomy and 18 underwent end-to-end uretero-ureteral anastomosis to repair the injury. Postoperatively 18 patients had a urinary tract infection. Hospital stay after reconstructive surgery ranged from 14 to 35 days (average 18). Long-term followup showed a normal upper urinary tract in 22 patients and mild to moderate hydroureteronephrosis in 2. Of the 20 patients who underwent percutaneous nephrostomy 16 (80%) had complete spontaneous recovery of the injured ureter after 14 to 66 days (average 32). Hospital stay after the insertion of the percutaneous nephrostomy tube ranged from 3 to 5 days. Urinary tract infection developed in 4 patients and mild hydronephrosis was noted in 1 on long-term followup. CONCLUSIONS: The primary management of ureteral injury by percutaneous nephrostomy resulted in significantly decreased reoperation and morbidity rates, and enabled spontaneous recovery of the injured ureter in the majority of patients.

Ectopic splenic tissue simulating a renal mass.

A 64-year-old patient who underwent splenectomy presented clinically with ectopic splenic tissue simulating a solid renal mass. The splenic origin of the mass was assessed by radionuclide spleen scan. Nephrectomy was avoided.

Testicular mass as a presenting symptom of isolated polyarteritis nodosa.

Isolated polyarteritis nodosa (PAN) of the male testes has rarely been reported. The authors describe two young men with testicular mass as a presenting symptom of isolated PAN, which was diagnosed following orchiectomy. The clinical features of the reported cases are reviewed.

Metachronous bladder tumors in patients with upper urinary tract transitional cell carcinoma.

Sixty-nine patients who underwent nephroureterectomy for upper urinary tract transitional cell carcinoma were included in the study. The following data were collected for each patient: grade and stage of renal/ureteral tumor, tumor location, timing of tumor appearance and recurrence in the bladder, grade and stage of each of the recurrent tumors, and number of recurrences. Follow-up ranged between 2 and 15 years. Thirty-three patients (47.8%) developed metachronous bladder tumors. The appearance of the bladder tumors was related to tumor grade and multifocality of the upper urinary tract TCC. Of the 33 patients, 19 had 1 tumor appearance in the bladder, 6 had 2 recurrences, and 8 had 3 recurrences. The 5-year survival rate for patients with no subsequent bladder tumors was 57% compared to 22% for those who had subsequent tumors. It is concluded that the appearance of bladder tumors following nephroureterectomy characterizes a group of patients with biologically more active disease with unfavorable prognosis.

Effect of improved diagnosis of renal cell carcinoma on the course of the disease.

The impact of the improved diagnosis of renal cell carcinoma (RCC) on the course of the disease was evaluated in 188 patients who were diagnosed and treated at a single medical center. Sixty-seven patients (group A) who had undergone nephrectomy between 1979 and 1983 for RCC initially diagnosed by intravenous pyelography (IVP) were compared with 121 patients (group B) who had undergone nephrectomy between 1983 and 1989, diagnosed by ultrasound and/or computed tomography (CT) scan. Incidental asymptomatic tumors were found in 18 of 67 (26.9%) group A patients and in 57 of 121 (47.1%) group B patients (P < 0.001). The incidence of small tumors of < 5 cm in diameter was significantly lower in group A compared to group B (25.4% vs. 47.9%, respectively, P < 0.01). The disease-free 5-year survival rate for group A was 40% compared to 80% for group B. It is concluded that the introduction of modern imaging techniques has improved the survival of patients with RCC and decreased the progression rate of the disease.

A comparison between digitally-guided fine needle aspiration and ultrasound-guided transperineal core needle biopsy of the prostate for the detection of prostate cancer.

OBJECTIVE: To prospectively examine the accuracy of fine needle aspiration (FNA) for the detection of prostate cancer. Ultrasound-guided core needle biopsy of the prostate was used as the standard to which the FNA results were compared. PATIENTS AND METHODS: One-hundred patients who had been referred for urological evaluation were suspected of having prostate cancer on the basis of digital rectal examination (DRE) and/or transrectal ultrasound (TRUS). All were further evaluated by digitally guided transrectal FNA and by TRUS-guided transperineal core needle biopsy. RESULTS: Prostate cancer was identified in 54 patients by core needle biopsy and in 45 by FNA. The sensitivity of FNA was 81% and both specificity and positive predictive value were 98%. CONCLUSION: FNA is easily performed, has negligible morbidity and offers prompt results. These data suggest that FNA is a reasonable initial diagnostic procedure for the detection of prostate cancer. Core needle biopsy may be reserved for patients with negative cytology who are clinically suspected of having prostate cancer. In selected patients, FNA may be used as an alternative to core needle biopsy for diagnosis, treatment planning and follow-up.

Rapid tumour recurrence following cessation of long-term treatment with intravesical thiotepa.

OBJECTIVE: To report tumour recurrence related to cessation of long-term therapy with thiotepa. PATIENTS AND METHODS: A group of 12 patients with low grade (I-II), low stage (TA-T1) transitional cell carcinoma of the bladder were included in the study. All patients had been treated with intravesical thiotepa for a period ranging from 24 to 71 months and none had had a recurrence for a period of between 15 and 51 months. After referral to this department all the patients were withdrawn from thiotepa therapy. RESULTS: All the patients developed bladder tumours within 6 months of cessation of therapy. The recurrent tumours were grade II in 10 patients and grade III in two patients. Eight patients had stage TA and four had stage T1. All responded to bacille Calmette-Guérin therapy and none had tumour recurrence on follow up at 24 months. CONCLUSION: Meticulous follow-up of patients is indicated soon after the cessation of long-term therapy with thiotepa.