The Scientific Basis of Urology

Cover......Page 1
The Scientific Basis of Urology......Page 4
Contents......Page 6
Contributors......Page 9
Preface to the first edition......Page 15
Preface to the second edition......Page 17
THE CELL MEMBRANE......Page 18
MEMBRANE TRANSPORT......Page 19
Intermediate filaments......Page 22
Tight junctions......Page 23
Microfilamentous junctions with the extracellular matrix......Page 24
THE EXTRACELLULAR MATRIX......Page 26
Glycosaminoglycans and proteoglycans......Page 27
THE BASEMENT MEMBRANE......Page 29
CELL TO CELL COMMUNICATION......Page 30
CELL TO CELL SIGNALLING......Page 31
CELL SURFACE RECEPTORS......Page 33
INOSITOL TRIPHOSPHATE AND CALCIUM......Page 38
TYROSINE KINASE RECEPTORS......Page 40
GROWTH FACTORS......Page 41
FURTHER READING......Page 46
Cell membrane......Page 48
Golgi apparatus......Page 50
Mitochondrial DNA......Page 51
Arrangement of DNA......Page 54
DNA replication errors......Page 55
Cell division (Figure 2.18)......Page 57
Anaphase......Page 58
THE CELL CYCLE......Page 59
The control of cell division......Page 60
Growth factors and the control of the cell cycle......Page 61
STRUCTURE OF DNA AND RNA......Page 62
mRNA synthesis......Page 65
Introns and exons: mRNA processing......Page 67
Modification of DNA can alter transcription......Page 68
PROTEIN SYNTHESIS......Page 69
CAUSES OF INFLAMMATION......Page 74
Neutrophil and leucocyte actions and activation in acute inflammation......Page 75
BACTERIAL KILLING......Page 78
CHEMICAL MEDIATORS OF ACUTE INFLAMMATION......Page 79
Interleukin-1 (IL-1)......Page 81
Monocytes and macrophages in acute inflammation......Page 82
Chemical signals that influence macrophage function......Page 83
Phagocytes......Page 84
Inflammatory mediators......Page 85
ADAPTIVE IMMUNITY......Page 87
T-cell recirculation......Page 88
Major histocompatibility antigens......Page 89
Helper or CD4+ T cells......Page 90
Cytotoxic or CD8+ T cells......Page 91
Immunoglobulin diversity......Page 92
Antibody-dependent, cell-mediated cytotoxicity......Page 93
Immunoglobulin superfamily members......Page 94
Co-stimulation......Page 95
Cancer immunotherapy......Page 96
REFERENCES......Page 97
The concept of external balance......Page 100
The concept of renal clearance......Page 101
FUNCTIONAL SEGMENTATION OF THE NEPHRON......Page 102
The function of the glomerulus......Page 103
GLOMERULAR FILTRATION......Page 104
Starling forces......Page 105
The ultrafiltration coefficient......Page 106
Factors affecting Kf......Page 107
Sodium reabsorption......Page 108
Effect of physical forces on proximal tubular reabsorption......Page 109
Phosphate......Page 110
Proximal tubular secretion of organic anions......Page 111
Tubuloglomerular feedback......Page 112
The afferent stimulus......Page 113
Intrarenal control of sodium excretion......Page 114
The efferent limb in the regulation of sodium excretion......Page 115
The kallikrein-kinin system......Page 116
The loop of Henle......Page 117
The distal convoluted tubule (DCT)......Page 118
Potassium excretion......Page 119
Potassium transport in the distal tubule and collecting duct......Page 120
Volatile and non-volatile acid......Page 121
Distal tubular H+ secretion......Page 122
Loop of Henle......Page 124
Renal handling of phosphate......Page 126
Renal metabolism of vitamin D......Page 127
Countercurrent multiplication and exchange......Page 128
Free water clearance and reabsorption......Page 129
REFERENCES......Page 130
Digital radiography and PACS......Page 134
Iodinated contrast media......Page 135
RADIATION HAZARDS......Page 136
Computerized tomography (CT)......Page 137
Spiral CT and volume or 3-D reconstruction......Page 138
Grey-scale ultrasound......Page 140
Spectral or duplex Doppler......Page 141
Therapeutic medical ultrasound......Page 142
Magnetic resonance imaging (MRI)......Page 143
MR angiography and spectroscopy......Page 144
FURTHER READING......Page 145
CLINICAL PRESENTATION......Page 146
Medical......Page 147
PHYSIOLOGICAL CHANGES......Page 148
Blood-flow and GFR changes......Page 149
INFLAMMATORY RESPONSE IN UO......Page 150
Role of individual cytokines in UO......Page 151
Cell signalling in apoptosis......Page 152
Clusterin......Page 153
p53......Page 154
THE CONTRALATERAL KIDNEY......Page 155
POST-OBSTRUCTIVE DIURESIS......Page 156
CONCLUSIONS......Page 157
REFERENCES......Page 158
HISTORICAL PERSPECTIVE......Page 164
THE MICTURITION CYCLE......Page 166
EFFECT OF BLADDER WALL HYPERTROPHY......Page 167
MEASUREMENT OF END VOID PRESSURE......Page 168
SUMMARY OF FILLING-PHASE ABNORMALITIES......Page 169
INTERACTIVE PRESSURE RECORDINGS IN PATIENTS WITH HIGH-PRESSURE CHRONIC RETENTION AND HYDROURETER/ HYDRONEPHROSIS......Page 170
Experimental observations......Page 172
EXCRETORY FUNCTION MEASURED BY GAMMA CAMERA RENOGRAPHY......Page 174
GRAVITATIONAL THEORY OF DRAINAGE......Page 175
BIOCHEMICAL STUDIES BEFORE AND AFTER THE RELIEF OF OBSTRUCTION......Page 178
FURTHER READING......Page 180
Colonizing micro-organisms in health......Page 182
General defence mechanisms......Page 183
HOST DEFENCE MECHANISMS—LOWER URINARY TRACT......Page 184
Bladder surface mucin......Page 185
Tamm-Horsfall protein......Page 186
Virulence against external agents—antimicrobial resistance......Page 187
Alteration of binding site......Page 188
Antihumeral activity......Page 189
Types of adhesins......Page 190
Supramolecular adhesins associated with pathogenic strains of E. coli......Page 191
Initiation of the infective process......Page 192
Structure and ultrastructure of P fimbriae......Page 194
Historical relevance of fimbrinated status......Page 195
Clinical aspects of adhesion theory......Page 198
Summary of virulence factors in urinary tract infections......Page 199
ORGANISMS RESPONSIBLE FOR URINARY TRACT INFECTION......Page 200
Ascending route......Page 201
The significance of ‘significance’......Page 202
The introital question......Page 203
Infants......Page 204
Pre-school children......Page 205
Bacteriuria during pregnancy......Page 206
The urethral syndrome......Page 207
Prostatitis......Page 208
Localization of infection......Page 209
Non-bacterial prostatitis......Page 210
Antibiotic penetration in prostatitis......Page 211
Tuberculosis......Page 212
Laboratory diagnosis......Page 213
Bacteraemia and septic shock......Page 214
Localization studies in the urinary tract......Page 215
REFERENCES......Page 216
INTRODUCTION......Page 222
STONE COMPOSITION......Page 223
Supersaturation......Page 225
Processes of crystallization......Page 227
CYSTINE STONE FORMATION......Page 228
URIC ACID STONE FORMATION......Page 231
INFECTED STONE FORMATION......Page 232
CALCIUM STONE DISEASE......Page 234
Prevention of stone recurrence......Page 238
REFERENCES......Page 240
PATHOPHYSIOLOGY OF SHOCK......Page 246
Cardiogenic shock......Page 247
Hypovolaemic shock......Page 248
Distributive shock......Page 249
Obstructive shock......Page 251
Pulmonary artery wedge pressure (PAWP)......Page 252
Correction of blood constituents......Page 253
Correction of a low stroke volume in cardiogenic shock......Page 254
Correction of blood pressure......Page 255
Reducing metabolic demand......Page 256
REFERENCES......Page 257
Presentation......Page 262
Biochemistry......Page 263
Differential diagnosis......Page 264
Specific treatment of underlying disease......Page 265
Introduction......Page 266
Glomerular filtration......Page 267
Vasoactive mediators......Page 268
Venous obstruction......Page 269
Free radicals......Page 270
Biochemical events during acute ischaemic cell injury......Page 271
REFERENCES......Page 272
Aetiology......Page 274
Mechanisms of progressive renal failure......Page 275
Consequences of progressive renal failure......Page 276
Water......Page 277
Anaemia......Page 278
Hyperparathyroidism......Page 279
Atherosclerosis......Page 280
REFERENCES......Page 281
THE STRUCTURE OF THE BLADDER AND URETHRA......Page 282
THE URETHRAL SPHINCTER MECHANISM......Page 288
THE INNERVATION OF THE BLADDER AND URETHRA......Page 290
Functional aspects of the innervation of the bladder and urethra......Page 291
OTHER NEUROTRANSMITTERS......Page 294
THE AFFERENT INNERVATION OF THE BLADDER......Page 295
CEREBRAL CONTROL OF VOIDING......Page 297
THE NORMAL BLADDER FILLING-VOIDING CYCLE......Page 299
WHAT KEEPS THE BLADDER PRESSURE LOW DURING FILLING?......Page 300
WHAT CAUSES THE RISE IN URETHRAL PRESSURE DURING BLADDER FILLING?......Page 301
HOW DOES THE BLADDER NECK OPEN?......Page 302
VESICO-URETHRAL REFLEXES......Page 303
SUMMARY......Page 304
REFERENCES......Page 305
Bladder intravesical pressure and detrusor wall tension......Page 308
Models of the bladder and stress-relaxation......Page 309
Isotonic contractions......Page 310
Smooth muscle energetics......Page 312
THE CONTRACTILE MACHINERY......Page 313
Role of motor nerves......Page 316
Breakdown of neurotransmitters in the synaptic cleft......Page 317
Muscarinic receptors and contractile activation......Page 318
Purinergic receptors and contractile activation......Page 319
Ion channels and membrane events......Page 320
Non-specific cation channels......Page 321
Ca2+-activated K+ channels......Page 322
The functions of ion channels in detrusor smooth muscle......Page 323
Propagation of electrical signals?......Page 324
REGIONAL DIFFERENCES IN BLADDER SMOOTH MUSCLE......Page 325
Adrenergic agents......Page 326
REFERENCES......Page 327
Bladder overactivity......Page 332
BLADDER INSTABILITY AND INCREASED MYOGENIC ACTIVITY—OUTLINE......Page 333
Response to muscarinic agonists......Page 334
Response to purinergic agonists......Page 335
Transmitter release......Page 337
Contractile activation......Page 338
PROPERTIES OF DETRUSOR SMOOTH MUSCLE—INTERCELLULAR COMMUNICATION......Page 339
REFERENCES......Page 340
PHYSICS AND MECHANICS OF THE LOWER URINARY TRACT......Page 344
Storage phase......Page 345
Voiding phase......Page 347
Cystometry......Page 348
Urethral pressure profilometry (UPP)......Page 349
Flowmetry......Page 350
Filling cystometry......Page 351
Flowmetry and voiding cystometry......Page 353
SYMPTOMS AND URODYNAMICS......Page 356
CONCLUSION: URODYNAMICS—ART OR SCIENCE?......Page 357
REFERENCES......Page 358
TESTOSTERONE METABOLISM......Page 360
HYPOTHALAMIC-PITUITARY-TESTICULAR AXIS......Page 361
THE PHYSIOLOGY AND PHARMACOLOGY OF PENILE ERECTION......Page 362
Haemodynamic phases of erection......Page 363
Tumescence phase......Page 364
Central control of penile erection......Page 365
Sensory pathways......Page 366
Acetylcholine (ACh)......Page 367
Endothelium-derived factors......Page 368
Pathophysiology of erectile dysfunction (ED)......Page 370
Ageing and ED......Page 371
Arteriogenic impotence......Page 372
Other causes of ED......Page 373
Pharmacological concepts of potency and selectivity of a drug......Page 374
FERTILITY......Page 375
Spermatozoa......Page 377
Testicular maldescent......Page 378
Sperm maturation......Page 379
Seminal analysis......Page 380
REFERENCES......Page 381
FURTHER READING......Page 382
The structure of the prostate......Page 384
Endocrinology of the prostate......Page 385
Growth factors in the prostate......Page 387
The role of the prostate in continence......Page 388
EMISSION AND EJACULATION......Page 389
The physiological function of prostatic secretion......Page 391
BENIGN PROSTATIC HYPERPLASIA......Page 392
Pathogenesis......Page 393
Urodynamic aspects......Page 397
REFERENCES......Page 400
CHEMICAL CARCINOGENESIS......Page 404
GENETIC POLYMORPHISMS......Page 405
Cancer genes......Page 406
CELLULAR CHARACTERISTICS OF CANCER......Page 407
METASTASIS......Page 408
Altered cell adhesion......Page 409
ACKNOWLEDGEMENT......Page 410
ONCOGENES......Page 412
Ras family......Page 413
Heterotrimeric G proteins......Page 414
Epidermal growth factor (EGF) and the EGF receptor (EGFR)......Page 417
Fibroblast growth factors (FGFs)......Page 418
TUMOUR SUPPRESSOR GENES......Page 419
p53 and G1 arrest......Page 420
Retinoblastoma gene......Page 421
ACKNOWLEDGEMENT......Page 422
THE PATHOLOGICAL AND GENETIC CLASSIFICATION OF ADULT RENAL EPITHELIAL NEOPLASMS......Page 424
Oncocytoma: epidemiology, macroscopic features and microscopic appearances......Page 425
Conventional RCC (C-RCC): the macroscopic and microscopic appearances of C-RCC......Page 427
Chromophobe RCC: epidemiology, and macroscopic, microscopic and ultrastructural appearances......Page 428
Sarcomatoid change......Page 429
Identification of the VHL tumour-suppressor gene......Page 430
Function of the VHL TSG product......Page 431
Non-VHL familial C-RCC (FCRC)......Page 432
The fumarate hydratase (FH) gene and familial type 2 papillary RCC (HPRC2)......Page 434
Tuberose sclerosis......Page 435
The mapping and identification of further RCC tumour suppressor genes: correlations with histopathological data......Page 436
Multiple TSGs on the short arm of chromosome 3 are central to non-P-RCC development......Page 437
Analysis of candidate TSGs in RCC: PTEN, the P53 pathway and RB......Page 438
REFERENCES......Page 439
Smoking......Page 448
Premalignant conditions......Page 449
Tumour grade......Page 450
Prognostic factors and natural history (Tables 23.4 and 23.5)......Page 451
Primary Tis......Page 452
HRAS......Page 453
RB1......Page 454
DBCCR1......Page 455
pRb and p53 pathways (Figure 23.2)......Page 456
Angiogenesis......Page 457
Immortalization......Page 458
NEW THERAPIES UTILIZING MOLECULAR TARGETS......Page 459
REFERENCES......Page 460
PATHOLOGY......Page 466
Histological grading......Page 467
Prostatic intraepithelial neoplasia......Page 468
Circulating PSA-positive cells in prostate cancer......Page 469
CLINICAL PRESENTATION......Page 470
Metastatic disease......Page 471
Gene therapy......Page 472
Apoptosis......Page 473
p53......Page 474
Transforming growth factor-beta 1 (TGF-β1)......Page 475
Epidermal growth factor (EGF)......Page 476
TUMOUR PLOIDY AND NUCLEAR MORPHOMETRY......Page 477
Androgen receptor (AR)......Page 478
MATRIX METALLOPROTEINASES (MMPS) AND THEIR INHIBITORS......Page 479
REFERENCES......Page 480
Testicular maldescent......Page 486
Factors favouring the importance of the intrauterine environment......Page 489
HEREDITARY FACTORS......Page 490
IDENTIFYING A TESTIS CANCER GENE......Page 491
Morphology and distribution......Page 493
Biomarkers of ITGCN......Page 494
Significance of the absence of ITGCN on biopsy......Page 495
Age of onset of ITGCN......Page 496
Immunocytochemistry as an adjunct to morphology in clinically relevant differential diagnosis......Page 497
Classification of testicular tumours and histological predictors of metastatic spread......Page 498
ASSESSMENT OF EXCISED TUMOUR MASSES AFTER CHEMOTHERAPY......Page 499
Human chorionic gonadotrophin (HCG)......Page 500
Placental alkaline phosphatase (PLAP)......Page 501
BASIS OF THE SENSITIVITY OF TESTICULAR TUMOUR TO DNA-DAMAGING AGENTS......Page 502
REFERENCES......Page 503
Electromagnetic radiation......Page 510
Particulate radiation......Page 511
Interactions of X-rays with matter......Page 512
Repair......Page 514
Reoxygenation......Page 516
PRINCIPLES OF RADIOTHERAPY TREATMENT......Page 517
Localization of the target volume......Page 518
Calculation of the dose distribution......Page 519
Side effects of treatment......Page 520
Brachytherapy......Page 521
REFERENCES......Page 522
Radiotherapy planning......Page 523
Tumour growth......Page 524
Cell killing......Page 525
DRUG RESISTANCE......Page 526
Multidrug resistance......Page 527
Early toxicity......Page 528
Late toxicity......Page 529
MEASURING EFFICACY......Page 530
INTENSIFYING TREATMENT......Page 531
Antibody therapy......Page 532
REFERENCES......Page 533
FERTILIZATION AND EARLY DEVELOPMENT OF THE HUMAN EMBRYO......Page 538
CHROMOSOMAL ABNORMALITIES: CLINICAL CONSIDERATIONS......Page 539
IMPLANTATION AND EARLY EMBRYONIC DEVELOPMENT......Page 540
EMBRYOLOGY OF THE UPPER URINARY TRACT......Page 541
CONGENITAL RENAL MALFORMATIONS: CLINICAL CONSIDERATIONS......Page 542
EMBRYOLOGY OF THE LOWER URINARY TRACT (BLADDER AND URETHRA)......Page 543
FUNCTIONAL DEVELOPMENT OF THE FETAL URINARY TRACT......Page 544
Female......Page 545
Male......Page 546
The testis......Page 548
GENITAL ANOMALIES: CLINICAL CONSIDERATIONS......Page 550
THE GENETIC BASIS OF GENITOURINARY MALFORMATIONS......Page 551
FUTURE APPLICATIONS OF DEVELOPMENTAL BIOLOGY......Page 552
REFERENCES......Page 553
NON-HEART-BEATING DONATION......Page 556
PRESERVATION SOLUTIONS......Page 557
ASSESSMENT OF LIVE DONOR......Page 558
ASSESSMENT OF THE RECIPIENTS......Page 559
MATCHING DONOR AND RECIPIENTS......Page 560
RENAL TRANSPLANTATION......Page 561
POST-TRANSPLANT MANAGEMENT......Page 562
REFERENCES......Page 563
The phases of wound healing......Page 566
GRAFTS AND FLAPS......Page 568
Grafts......Page 569
Flaps......Page 570
Intestinal flaps in bladder reconstruction......Page 571
Metabolic changes......Page 573
Urinary infection and malignant transformation......Page 574
Stones......Page 575
REFERENCES......Page 576
ELECTROMAGNETIC ENERGY......Page 578
The effect of EMR upon living tissue......Page 579
Radio frequency (RF)......Page 580
Microwaves......Page 581
Microwave prostatic therapies......Page 582
The properties of laser light......Page 583
Laser-tissue interactions......Page 585
Laser delivery systems......Page 586
General principles......Page 587
Lithotriptor design......Page 588
Application of ESWL......Page 590
Ultrasound probes......Page 591
Mechanical lithotripsy......Page 592
REFERENCES......Page 593
HISTORY OF UROLOGICAL ENDOSCOPES......Page 596
Contemporary telescope design......Page 597
Fibre-optic technology......Page 598
Lower urinary tract......Page 599
Analogue technology......Page 601
Three-dimensional (3-D) imaging......Page 602
Virtual reality......Page 603
REFERENCES......Page 604
MEDICAL HISTORY......Page 606
Cardiovascular disease......Page 607
Metabolic conditions......Page 608
Diseases of the nervous system......Page 609
Laboratory tests (Figure 33.4)......Page 610
Deep-vein thrombosis prophylaxis14......Page 611
Drug medication 21,22......Page 612
Major complex procedures—such as radical cystectomy and nephrectomy......Page 617
Percutaneous nephrolithotomy......Page 618
Myocardial events......Page 619
Respiratory failure (Figures 33.7 and 33.8)......Page 620
REFERENCES......Page 621
Selective screening......Page 624
LIFETIME EVENTS AND SCREENING TERMINOLOGY......Page 625
FUNDAMENTALS OF SCREENING......Page 626
ETHICAL CONSIDERATIONS AND ATTITUDES TO SCREENING......Page 627
The validity of screening tests......Page 628
Checking the sensitivity of a test......Page 630
PROGRAMME VALIDITY......Page 631
SCREENING AND CONTROL OF DISEASE......Page 633
GENERAL PRINCIPLES RELATING SCREENING PROGRAMMES......Page 634
Single-shot screening......Page 636
Bladder cancer......Page 637
Prostate cancer......Page 638
REFERENCES......Page 640
EARLY CLINICAL TRIALS......Page 642
TRIAL DESIGN......Page 643
NON-RANDOM AND SYSTEMATIC ALLOCATION......Page 644
SIZE OF A TRIAL......Page 645
Comparison of means (paired data, e.g. cross-over trial)......Page 646
PILOT STUDY......Page 647
GUIDELINES FOR THE CRITICAL APPRAISAL OF PUBLISHED CLINICAL TRIAL PAPERS......Page 648
THE CONSORT STATEMENT......Page 649
REFERENCES......Page 650
36 Evidence-based medicine for urologists......Page 652
THE CASE FOR EVIDENCE-BASED MEDICINE......Page 653
ASKING THE RIGHT QUESTIONS......Page 654
GETTING HOLD OF THE BEST EVIDENCE......Page 655
APPLYING EVIDENCE......Page 656
GETTING STARTED WITH EVIDENCE-BASED MEDICINE......Page 658
Other reliable sources......Page 659
Journals of secondary publication......Page 660
How to calculate an NNT......Page 661
TEXTBOOKS ON EVIDENCE-BASED MEDICINE......Page 662
REFERENCES......Page 663
Index......Page 664