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Biomedical subjects

M Abdel-Gawad

Publications and source records attributed to M Abdel-Gawad.

13 recordsLinked to original sources
PubMed2002

Modulation of insulin-like growth factor-I system of the bladder using a somatostatin analogue in chronic spinalized rats.

PURPOSE: We have previously reported the possible role of the insulin-like growth factor-I (IGF-I) system of mitogens in the development of detrusor smooth muscle hyperplasia and hypertrophy after spinal cord injury. We evaluated the in vivo effects of the anti-growth factor somatostatin analogue octreotide on the IGF-I system as well as subsequent changes in bladder smooth muscle hypertrophy and function after spinal cord injury in rats. MATERIALS AND METHODS: Included in this study were 90 adult female Sprague-Dawley rats weighing 200 to 250 gm. Of the rats 18 served as sham operated controls, while the remaining 72 underwent were spinal cord transection at the level of the T10 vertebra. The spinalized animals were randomly divided into 4 equal groups of 18, of which 1 group served as paraplegic controls. The other 3 groups received octreotide (60 microgram. daily for 4 weeks) delivered via a subcutaneously implanted osmotic pump immediately, 2 and 4 weeks after spinal cord injury. At the end of the experiment (6 to 8 weeks) each group of animals was subdivided into 2 subgroups of 9. In the first group filling cystometrography was done, while in the second subgroup wet bladder weight was estimated and Northern blot analysis was performed. RESULTS: Mean wet bladder weight plus or minus standard deviation in sham operated and paraplegic controls was 0.11 +/- 0.01 and 0.64 +/- 0.33 gm., respectively (p <0.05). The increase in bladder weight in paraplegic controls was associated with over expression of the IGF-I gene and with marked suppression of IGF binding proteins-3 and 5 compared with sham operated controls. On the other hand, mean wet bladder weight in the animals that received octreotide immediately after spinal cord injury was 0.17 +/- 0.02 gm., which was associated with a dramatic decrease in IGF-I gene expression and increased expression of IGF binding proteins-3 and 5. Mean cystometric bladder capacity in paraplegic controls was 0.48 +/- 0.18 ml. with an associated voiding pressure of 71 +/- 13 cm. water. All paraplegic controls showed detrusor hyperreflexia. In animals that received octreotide immediately after spinal cord injury mean cystometric bladder capacity was 2.49 +/- 1.75 ml. with an associated voiding pressure of 32 +/- 7 cm. water. Detrusor hyperreflexia disappeared in 88.89% of the rats in this group. There were less marked changes in bladder weight (mean 0.24 and 0.29 +/- 0.3 gm.), IGF-I gene expression and its binding proteins and urodynamic parameters when the drug was given 2 and 4 weeks, respectively, after spinal cord injury. CONCLUSIONS: Modulating the IGF-I system of mitogens in detrusor smooth muscle with consequently decreased bladder hypertrophy and improved urodynamic behavior in spinal cord injured animals using somatostatin analogue could be a possible therapeutic modality in patients with spinal cord injury.

Animals↗
PubMed2001

Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo experience.

OBJECTIVE: To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative) assay. METHODS: Urine samples of 149 individuals were tested for the presence of the human complement factor H-related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate cancer, and 65 patients with histologically proven bladder cancer. All samples were obtained prior to surgery or therapy. RESULTS: The BTA stat test was positive in 64 of 65 samples from patients with bladder cancer, for an overall sensitivity of 99%. With a BTA TRAK assay cut-off of 60 U/ml (set at 97% specificity in the healthy population), the sensitivity of the TRAK assay was 94%. There was no statistically significant difference between the sensitivities of the two BTA tests in patients diagnosed with squamous cell carcinoma and those with transitional cell carcinoma. The overall specificity of the BTA stat test was 67% ranging from 15% in patients with bilharziasis to 94% in healthy volunteers. The overall specificity of the TRAK assay was 66%, again with negative results in 15% of the patients with bilharziasis. CONCLUSIONS: The BTA stat test and TRAK tests are extremely sensitive in the detection of bladder cancer in the Egyptian population. Positive results (85%) are also observed in patients with active bilharziasis, which often leads to bladder cancer. Longitudinal follow-up of these positive cases is needed to determine whether these positive results are false or predictive of bladder cancer.

Adult↗
PubMed2001

Evidence of a peripheral role of neurokinins in detrusor hyperreflexia: a further study of selective tachykinin antagonists in chronic spinal injured rats.

PURPOSE: Spinal cord injury above the sacral micturition center usually leads to detrusor hyperreflexia, increased intravesical pressure and post-void residual urine. Detrusor hyperreflexia is believed to be mediated by afferent C fibers with tachykinins as neurotransmitters. We investigated the selective peptide tachykinin antagonists MEN 11420 and GR 82334 of NK-2 and NK-1 receptors, respectively, in a chronic rat model of detrusor hyperreflexia after suprasacral spinal cord injury. MATERIALS AND METHODS: Adult female Sprague-Dawley rats weighing 200 to 250 gm. were used. The spinal cord was transected at the T10 level. The bladder was evacuated by the Credé maneuver 3 times daily. After 6 weeks the rats were implanted with femoral vein and bladder dome catheters 2 days before filling cystometry. The 5 rats in group 1 received 100 nmol./kg. of the NK-2 antagonist MEN 11420 intravenously. The 5 rats in group 2 received 100 nmol./kg. of the NK-1 antagonist GR 82334 intravenously. The 5 rats in group 3 received a combination of the same dose of each antagonist. Three repetitive micturition cycles were recorded before injection. Three micturition cycles were done 20 minutes after the injection of each antagonist. Mean cystometric parameters were reported, including bladder capacity, micturition pressure, baseline pressure, post-void residual urine and micturition volume, and the number and amplitude of hyperreflexic contractions greater than 15 cm. water. RESULTS: MEN 11420 significantly reduced the frequency of hyperreflexic contractions and baseline bladder pressure (p <0.05). There was no statistically significant effect on the other cystometric parameters. GR 82334 reduced the amplitude of hyperreflexic contractions but not statistically significant. A combination of MEN 11420 and GR 82334 significantly reduced the frequency and amplitude of hyperreflexic contractions (p <0.05) with no significant effects on other cystometric parameters, although there was a tendency toward increased micturition volume and bladder capacity. CONCLUSIONS: These results suggest that at the peripheral level there is an efferent role of tachykinins in detrusor hyperreflexia after spinal cord injury. NK-1 and NK-2 receptor selective antagonists reduced the frequency and amplitude of hyperreflexic contractions as well as baseline bladder pressure. This finding may lead to potential new therapeutic modalities using selective tachykinins antagonists with other pharmacological agents to combat detrusor hyperreflexia.

Animals↗
PubMed2001

Reduction of bladder outlet resistance by selective stimulation of the ventral sacral root using high frequency blockade: a chronic study in spinal cord transected dogs.

PURPOSE: The use of electrical neural stimulation as treatment for neurogenic bladder is complicated by simultaneous contraction of the striated sphincter. This result is due to the composition of the ventral sacral roots, which contain somatic fibers innervating the external urethral sphincter and preganglionic parasympathetic fibers innervating the detrusor, among others. The somatic fibers have a larger caliber than the parasympathetic fibers and, as large diameter fibers, need a lower stimulus amplitude for activation than smaller fibers. Activation of the smaller fibers is always accompanied by activation of the larger fibers. We studied the effect of chronic application of selective combined low and high frequency current stimulation of the ventral sacral root on bladder evacuation and urethral resistance in chronically spinalized (spinal cord transected above the spinal micturition center) male dogs for daily bladder evacuation. MATERIALS AND METHODS: A total of 14 male mongrel dogs weighing 20 to 25 kg. underwent transection of the spinal cord at the T10 vertebra. The S2 ventral sacral root was wrapped with a bipolar electrode connected to a subcutaneous microstimulator. Daily bladder evacuation by neural stimulation with determination of the voided and residual urine volumes was done for 8 months. The animals were stimulated only with low frequency current during the 1-month spinal shock phase. Selective parameters of combined low frequency stimulation and high frequency blockade currents were subsequently applied for 6 months. For the last study month the animals were again stimulated by low frequency current alone. Bladder and urethral pressure as well as electromyography of the external urethral sphincter and pelvic floor muscles were evaluated monthly. Histopathological testing of the chronically stimulated nerve and external sphincter was performed. RESULTS: Of the 14 dogs 12 completed the followup study. During the shock phase with the application of low frequency only stimulation the animals voided 26% of mean functional bladder capacity with the early return of detrusor activity. Mean detrusor pressure plus or minus standard error of mean was 76.4 +/- 21.6 cm. water, while mean urethral pressure was 83.6 +/- 16.8 cm. water. During the application of selective combined low and high frequency stimulation 7 animals (58%) evacuated the bladder completely with post-void residual urine less than 10% of mean individual functional bladder capacity and 5 (42%) had mean post-void residual urine less than 20% of mean individual bladder capacity. Mean detrusor pressure was 73.5 +/- 20 cm. water and mean urethral pressure was 44 +/- 7.3 cm. water. There was a 45.19% reduction in the mean electromyography activity of the external sphincter. Stimulation of the dogs for the last month by low frequency current resulted in the voiding of 33% of mean bladder capacity with an increase in mean urethral pressure and electromyography activity. CONCLUSIONS: These results of reducing external sphincter activity by the simultaneous application of high frequency current blockade of the somatic fibers and activation of the autonomic fibers of the bladder by low frequency stimulation are promising.

Animals↗
PubMed2000

Implantable selective stimulator to improve bladder voiding: design and chronic experiments in dogs.

Among the treatments to enhance the bladder voiding, the sacral roots neurostimulation is one of the most promising techniques. The electrostimulation of sacral nerves provokes a simultaneous contraction of the detrusor muscle as well as the external urethral sphincter (EUS). A new simplified-architecture implantable stimulator with its wireless controller have been designed to investigate high-frequency inhibition stimulation strategies. This innovative technique based on high-frequency inhibition reduces sphincter activity during stimulation. Low-frequency current pulses also applied to the sacral roots induces contraction of the detrusor muscle resulting in low pressure voiding. Chronic experiments were carried out on ten male mongrel paraplegic dogs. One cuff electrode was implanted along with each stimulator for eight months. The animals were stimulated twice a day using the prototypes of our implantable selective stimulator while voided and residual urine volume were measured during the procedure. These experiments revealed that the proposed stimulation strategy enhances bladder voiding by more than 50% in comparison with low-frequency only stimulation. The residual urine volume was reduced to an average of 9% and low pressure micturition was achieved as shown by weekly cystourethrogram.

Animals↗
PubMed1999

The impact of chronic renal failure on nitric oxide synthase isoforms gene expression in the penis and pelvic ganglia of rats.

PURPOSE: Patients with chronic renal failure experience a variety of physical and metabolic alterations. Uremia is often accompanied by erectile dysfunction (ED). Little information is available concerning the underlying pathophysiological mechanisms by which chronic renal failure can lead to erectile dysfunction. In this study, chronic renal failure was induced by 5/6 nephrectomy in a rat model. Cavernous nerve stimulation was used to measure the intracavernous pressure (ICP) rise. MATERIALS AND METHODS: Adult male Sprague-Dawley rats, aged between 10-12 weeks and weighing 200-250 gm. were divided into two groups. The first group (n = 20) served as a control (sham-operated) and underwent laparotomy with dissection of the perirenal fat around both kidneys. The second group (n = 40) were subjected to an excisional 5/6 nephrectomy (unilateral nephrectomy and contralateral upper and lower polar nephrectomy). Serum creatinine was measured 3 days post-operatively and at the end of the 12th week. Development of renal failure was considered if the animal had serum creatinine more than 120 microM/l. After 12 weeks, 10 animals per group were subjected to electric field stimulation (EFS) of the cavernous nerve with simultaneous recording of ICP-rise and systemic blood pressure. Northern and western blot analyses were used to determine the mRNA expression and protein contents of NOS isoforms (neuronal and endothelial) in the penile tissues and MPG. RESULTS: This remnant kidney model resulted in renal failure in 20 of 40 animals. The ICP-rise after cavernous nerve stimulation in the renal failure group was significantly impaired, 7.7+/-2.9 cm. H2O, as compared to control rats, 55.5+/-1.2 cm. H2O (p<0.001). The latency period after cavernous nerve stimulation was significantly increased in renal failure rats (6.9+/-0.95 sec.) in comparison to controls (2.4+/-0.25 sec.). Six of ten uremic animals had significantly lower testosterone (<1 nmol./l.) levels compared to non-uremic rats (3.6 nmol./l.) (p<0.005). Northern blot analysis revealed that renal failure rats had significantly higher levels of nNOS mRNA in the MPG and penile tissues than controls. There was no change in eNOS mRNA in either group. Western blot analysis demonstrated that eNOS and nNOS protein contents in the MPG and penile tissues of renal failure rats were significantly higher than those of controls. CONCLUSION: This report demonstrates that impairment of erection in renal failure rats, as determined by ICP-rise, was present in spite of elevated neuronal nitric oxide synthase mRNA and its protein in the MPG and penile tissues. Further studies are needed to determine whether erectile dysfunction is a result of post-translational changes, circulating inhibitory substances or other factors.

Animals↗
PubMed1999

Experimental Chronic Renal Failure-Associated Erectile Dysfunction: Molecular Alterations in Nitric Oxide Synthase Pathway and IGF-I System.

Chronic renal failure causes wide-ranging disturbances in male erectile function, and the dysfunction usually is not corrected by hemodialysis. In this study, erectile function and expression of nitric oxide synthase (NOS) isoforms, insulin-like growth factor-I (IGF-I), and IGF-I binding proteins were assessed in rats in which uremia had been produced by 5/6 nephrectomy. In the animals that suffered renal failure, there was a significantly lower rise in intracavernosal pressure in response to electrical stimulation, and the mean patency period after cavernous nerve stimulation was significantly increased. The amount of neuronial NOS mRNA was significantly higher in the penile tissues and major pelvic ganglia (MPG) of uremic rats than in control animals. There consistently were higher levels of nNOS and endothelial NOS in the penile tissues and MPG of rats with renal failure, and there was a significant decrease in the amount of IGF-I gene expression in the MPG of these animals. Expression of the IGF binding proteins 2 and 4 but not 5 also was reduced. This preliminary work demonstrates that impairment of erection in chronic renal failure in the rat is attributable to a disturbance in NOS gene expression with concomitant changes in IGF-I. These discoveries may permit an improved therapeutic approach to men with erectile dysfunction associated with chronic renal failure.

Journal Article↗
PubMed1999

Alteration of the insulin-like growth factor system of mitogens in hyperplastic bladders of paraplegic rats.

PURPOSE: Smooth muscle cells of the bladder retain the ability to proliferate in response to injury or mechanical stimulation. Insulin-like growth factor (IGF) I is a mitogenic and hypertrophic agent for smooth muscle cells. The purpose of this study is to examine if spinal cord injury could lead to bladder hypertrophy via the IGF system. MATERIALS AND METHODS: The study involved spinal cord transection of female Sprague Dawley rats (approximately 250 to 300 gm.). Six weeks following surgery the urinary bladder was collected. Northern and Western blotting, and IGF-I receptor (IGF-IR) affinity labeling were used to determine the expression of the IGF system, IGFBP levels, and IGF-IR levels respectively. RESULTS: Chronic spinal cord injury leads to an increase in the wet weight of the bladder and in the level of proliferation cell nuclear antigen expression. IGF-I mRNA levels increase, while IGFBP 3 and 5 mRNA and protein levels dramatically decrease. The gene expression of IGFBP 2 and 4 varies from rat to rat, and IGF-IR expression slightly increases. CONCLUSION: Our results suggest that following spinal cord injury, overexpression of IGF-I and underexpression of IGFBP 3 and 5 may lead to hyperplasia of the smooth muscle layer of the bladder.

Animals↗
PubMed1998

Implantable stimulation system dedicated for neural selective stimulation.

A functional electrical stimulation system is presented, which is dedicated for the selective neural stimulation of the bladder. The proposed system is composed of an internal stimulator (implant) and an external controller. The system is used to produce low-pressure voiding of the bladder in spinal cord injured patients. The implant is powered and operated by the external controller via radio-frequency electromagnetic coupling. All stimulation parameters are chosen externally using the controller and are sent to the implant, which produces the desired stimuli. These stimuli are applied directly to the S2 nerve which is linked to the sphincter and bladder muscles. A high-frequency signal is used to inhibit the contraction of the sphincter muscle, and low-frequency pulses stimulate the bladder muscle (the detrusor). Dedicated computer software is used by the physician to select the optimal parameters for each patient and to activate the implant through a parallel port interface with built-in transmitter. The parameters are then transferred to a hand-held controller which is used by the technical staff and by the patients themselves. Acute studies have been performed to validate the selective stimulation strategy, and chronic experimentation is currently underway in dogs.

Electric Stimulation Therapy↗
PubMed1996

Clinical, radiological and histological features of adrenal myelolipoma: review and experience with a further eight cases.

OBJECTIVE: To review published reports of surgically treated adrenal myelolipomas and report experience with a further eight cases. PATIENTS AND METHODS: Eight patients (three men and five women, mean age 50.7 years) with adrenal myelolipoma were treated surgically because of the tumour size, symptomatology and/or associated renal pathology. Associated medical problems included hypertension in three patients and diabetes mellitus in one but none of the tumours was endocrinologically active. RESULTS: Five patients were diagnosed definitively by abdominal ultrasonography, computed tomography and angiography while the other three were incidentally diagnosed during surgical intervention for ipsilateral renal cell carcinoma in one patient, hydronephrotic kidney in another and multiple renal stones in the third. On pathological examination, the masses removed were surrounded by a thin fibrous capsule and compressed cortical tissue. A cut section was bright yellow with foci of red-brown discoloration. Microscopically, the tumour consisted mainly of mature adipose tissue with scattered islands of haemopoietic cells. There was no operative mortality and no gross morbidity. CONCLUSION: The management of adrenal myelolipoma should be appropriate to each individual case. Operative intervention should be reserved for symptomatic patients or those with large 'silent' tumours that may produce life-threatening shock secondary to spontaneous haemorrhage. Small asymptomatic tumours with definite radiological findings can be followed expectantly.

Adrenal Gland Neoplasms↗
PubMed1995

Prostatic abscess in a child.

We report a metastatic prostatic abscess in a 12-year-old boy. Rectal examination revealed a tender, fluctuating prostatic mass, causing acute retention of urine. Prostatic imaging by computerized tomography and transrectal ultrasonography were important in the diagnosis and management.

Abscess↗