- Email: [email protected]
BLADDER INSTABILITY OR URETHRAL CAUSES?
976
P-lactamase inhibitor to be implicated as an enzyme inducer, p-lactam agents and (3-lactamase inhibitors will variably induce class 1 (3-lactamase in gram-negative bacilli in vitro according to the compound and the bacterial strain under test.5 However, the phenotypic expression of stable p-lactam multiresistance has been associated with stably derepressed variants6 and may be regarded as characteristic of such strains (Dr W. W. Nichols, Public Health Laboratory Service). Hence we believe that derepressed mutant selection was probably the important mechanism in our case. Certainly weight is added to the arguments3’ against the theory that compounds with low inducing power, such as those containing P-lactamase inhibitors, offer potential therapeutic advantages by making class 1 p-lactamase-mediated resistance unlikely to develop. Depite previous reports’ our experience suggests that serious gram-negative infections should not be treated with timentin alone but only in combination with another antibiotic, for
example, We
are
an
aminoglycoside.
grateful to Dr T.
L. Pitt for
typing the strains of Ps aeruginosa.
Institute of Pathology
R. G. MASTERTON P. J. GARNER N. A. HARRISON D. J. RAINFORD
and Tropical Medicine, Department of Renal Medicine, Princess Mary’s Hospital, RAF Halton,
Aylesbury, Bucks HP22 5PG
MJ, Perinpanayagam RM. Test for &bgr;-lactamase production. Lancet 1985; ii. 673-74 Sanders CC, Sanders WEJ Emergence of resistance during therapy with the newer &bgr;-lactam antibodies: Role of inducible &bgr;-lactamase and implications for the future. Rev Infect Dis 1983, 5: 639-48. Phillips I Beta-lactamase induction and derepression. Lancet 1986; i 801-02. Livermore DM. Class I &bgr;-lactamase expression in Pseudomonas aeruginosa and cephalosporins resistance. Lancet 1986; i 450. Farmer TH, Reading C. Induction of the &bgr;-lactamases of a strain of Pseudomonas aeruginosa, Morganella morganu and Enterobacter cloacae J Antimicrob Chemother
1. Weinbren 2.
3. 4.
5
1987; 19: 401-04. WW, Milne LM. Derepressed &bgr;-lactamase synthesis in strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. J Antimicrob Chemother 1986; 18: 549-50. 7. Bru JP, Michallet M, Legrand C, et al A prospective randomised study comparing the efficiency of Timentin alone or in combination with amikacin in the treatment of febrile neutropenic patients. J Antimicrob Chemother 1986; 17 (suppl C): 203-09. 6. Nichols
neck" far more often reflects a response to obstruction than a primary disease.10 Despite the above, your editorial mentions neither "urethra" nor "obstruction". Cystometry is a weak diagnostic reed; nonneuropathic "bladder instability" is a sign, not a disease; and missing a urethral disorder all too often needlessly consigns children to years of drug-taking, symptoms, and, sometimes, more serious consequences.
SAMUEL J. ARNOLD ARTHUR GINSBURG DAVID L. TAYLOR
Adult and Pediatric Urology Group, 11 Pine Street, Morristown, New Jersey 07960, USA
1.
Borzyskowski M, Mundy AR. Videouredynamic
assessment
of diurnal urinary
incontinence. Arch Dis Child 1987; 62: 128-31. 2 Quist ES, Kirstensen ES, Nielson KK, et al. Detrusor
instability in children with infection and enuresis. Urol Internat 1986; 41: 196-98. 3. Sorensen SS, Nielsen JB, Norgaard JP, Knudsen LM, Djurhuus JC. Changes in bladder volume with repetition of water cystometry. Urol Res 1984, 12: 205-08. 4. Hunter J (1856). Cited by Speakman MJ, Sethia KK, Fellows GJ, Smith JC. A study of the pathogenesis, urodynamic assessment and outcome of detrusor instability associated with bladder outflow obstruction. Br J Urol 1987; 59: 40-44 5. Lyon RP, Marshall S. Urinary tract infections and difficult urination in girls: Long-term follow-up. J Urol 1971; 105: 314-17. 6. Hendren WH. Postenor urethral valves in boys: a broad clinical spectrum J Urol 1971, 106: 298-307. 7. Mahony DT, Laferte RO. Studies of enuresis VII. Results of distal internal urethrotomy in girls with juvenile urinary incontinence. Urology 1974, 4: 162-72 8. Arnold SJ, Ginsburg A. Radiographic and photoendoscopic studies in posterior urethral valves in enuretic boys. Urology 1974, 4: 145-54. 9. Mundy AR. The unstable bladder. Urol Clin N Am 1985; 12: 317-28. 10. Palmtag H. The site of functional infravesical obstruction in children Bri J Urol 1983; 55: 395-401. recurrent urinary tract
EPIDERMAL CELLS IN CULTURE
SIR,-Dr Blair and colleagues (Aug 29, p 483) state that epithelial cell culture techniques (for preparing epidermal grafts) "present almost insurmountable difficulties in maintenance of sterility and prevention of fibroblast overgrowth". In this laboratory, grafts composed of epidermal cells have been grown in culture for the treatment of bums,’ leg ulcers, and congenital naevi. Other centres have also reported the successful use of cultured epithelium in the ofburns,2-s leg ulcers,6 junctional epidermolysis bullosa,7 split thickness skin graft donor sites.8 Under proper culture conditions, microbial contamination is very rare. It is the patient who is regularly contaminated, but that is a problem for the surgeon not the cell biologist. The presence of appreciable numbers of fibroblasts is unusual in 3T3-supported cultivation but can easily be controlled by selective detachment of the fibroblasts with edetic acid (EDTA).9 Far from being insurmountable, these problems are hardly worth mentioning if cultivation is properly carried out. The successful use of this technique throughout the world suggests a very promising future for its clinical use. treatment
and
BLADDER INSTABILITY OR URETHRAL CAUSES?
SiR,-Diurnal and nocturnal enuresis, urinary frequency, and urgency in children are often attributed to psychological causes, and your Aug 8 editorial (p 314) does well to draw attention to the fact
studies in such children bladder capacity, bladder trabeculation, reflux, and, most commonly, detrusor instability and a wide bladder neck. Unfortunately, you uncritically accept the diagnosis of "bladder instability" and underplay urethral causes for the problems discussed. A diagnosis of bladder instability relies upon cystometry, and cystometry is not always reliable or reproducible z3 Nor does it reveal urethral obstruction, sensation, or activity. As a test of lower urinary tract function or disease, therefore, it remains at best incomplete, at worst wholly misleading. The test merely reveals a sign, and it is a mistake to treat a sign as a disease. The ability of bladder events to produce the symptoms under discussion has been over-rated. Increased bladder pressure, bladder contractions, and bladder instability do not necessarily result in symptoms. The bladder cannot produce incontinence without urethral cooperation. Extensive and weighty evidence supports urethral disease as a cause of the voiding symptoms and organic findings reported. In 1856 John Hunter’ commented on the connection between urinary frequency, bladder trabeculation, and obstruction. Dilatation of fibrous distal urethral segment totally cured 88% of 104 girls suffering with non-infectious "... day wetting urgency and frequency".5 Such symptoms are almost always relieved by adequate urethral treatment.6-8 Obstruction remains the only proven cause of non-neuropathic instability.9 The "wide bladder
that urodynamic frequently reveal
and low
radiographic functional
Department of Physiology and Biophysics, Harvard Medical School, Boston, Massachusetts 02115, USA
TANIA PHILLIPS OLANIYI KEHINDE
NE, Mulliken JB, Banks-Schlegel S, Kehinde, O, Green H Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet 1981, i: 75-78. Pittelkow MR, Scott RE. New techniques for the in vitro culture of human skin keratinocytes and perspectives on their use for grafting of patients with extensive bums Mayo Clin Proc 1986; 61: 771-77. Hefton JM, Madden MR, Finkelstein JL, Shires GT. Grafting of burn patients with allografts of cultured epidermal cells Lancet 1983; ii. 428-30. Cuono C, Langdon R, McGuire J. Use of cultured epidermal autografts and dermal allografts as skin replacement after bum injury. Lancet 1986, i 1123-24 Teepe R, Ponec M, Kreis RW, Hermans RP Improved method for treatment of burns with autologous cultured human epithelium. Lancet 1986, i 385 Phillips T, Leigh IM, Hackett H, et al. Allografts of cultured keratinocytes m clinical
1. O’Connor
2.
3 4.
5 6.
Br J Dermatol 1986; 115: 21-22 Lin AN, Varghese MC, et al. Treatment of junctional epidermolysis bullosa with epidermal autografts. J Am Acad Dermatol 1987, 17: 246-50 8. Thivolet J, Faure M, Demiden A, Mauduit G. Long term survival and immunological tolerance of human epidermal allografts produced in culture. Transplantation 1986; practice.
7. Carter
DM,
47: 274-80. 9. Sun T-T, Green H. Differentiation of the epidermal keratinocyte formation of the cornified envelope Cell 1976, 9: 511-21.
in
cell culture
P-lactamase inhibitor to be implicated as an enzyme inducer, p-lactam agents and (3-lactamase inhibitors will variably induce class 1 (3-lactamase in gram-negative bacilli in vitro according to the compound and the bacterial strain under test.5 However, the phenotypic expression of stable p-lactam multiresistance has been associated with stably derepressed variants6 and may be regarded as characteristic of such strains (Dr W. W. Nichols, Public Health Laboratory Service). Hence we believe that derepressed mutant selection was probably the important mechanism in our case. Certainly weight is added to the arguments3’ against the theory that compounds with low inducing power, such as those containing P-lactamase inhibitors, offer potential therapeutic advantages by making class 1 p-lactamase-mediated resistance unlikely to develop. Depite previous reports’ our experience suggests that serious gram-negative infections should not be treated with timentin alone but only in combination with another antibiotic, for
example, We
are
an
aminoglycoside.
grateful to Dr T.
L. Pitt for
typing the strains of Ps aeruginosa.
Institute of Pathology
R. G. MASTERTON P. J. GARNER N. A. HARRISON D. J. RAINFORD
and Tropical Medicine, Department of Renal Medicine, Princess Mary’s Hospital, RAF Halton,
Aylesbury, Bucks HP22 5PG
MJ, Perinpanayagam RM. Test for &bgr;-lactamase production. Lancet 1985; ii. 673-74 Sanders CC, Sanders WEJ Emergence of resistance during therapy with the newer &bgr;-lactam antibodies: Role of inducible &bgr;-lactamase and implications for the future. Rev Infect Dis 1983, 5: 639-48. Phillips I Beta-lactamase induction and derepression. Lancet 1986; i 801-02. Livermore DM. Class I &bgr;-lactamase expression in Pseudomonas aeruginosa and cephalosporins resistance. Lancet 1986; i 450. Farmer TH, Reading C. Induction of the &bgr;-lactamases of a strain of Pseudomonas aeruginosa, Morganella morganu and Enterobacter cloacae J Antimicrob Chemother
1. Weinbren 2.
3. 4.
5
1987; 19: 401-04. WW, Milne LM. Derepressed &bgr;-lactamase synthesis in strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. J Antimicrob Chemother 1986; 18: 549-50. 7. Bru JP, Michallet M, Legrand C, et al A prospective randomised study comparing the efficiency of Timentin alone or in combination with amikacin in the treatment of febrile neutropenic patients. J Antimicrob Chemother 1986; 17 (suppl C): 203-09. 6. Nichols
neck" far more often reflects a response to obstruction than a primary disease.10 Despite the above, your editorial mentions neither "urethra" nor "obstruction". Cystometry is a weak diagnostic reed; nonneuropathic "bladder instability" is a sign, not a disease; and missing a urethral disorder all too often needlessly consigns children to years of drug-taking, symptoms, and, sometimes, more serious consequences.
SAMUEL J. ARNOLD ARTHUR GINSBURG DAVID L. TAYLOR
Adult and Pediatric Urology Group, 11 Pine Street, Morristown, New Jersey 07960, USA
1.
Borzyskowski M, Mundy AR. Videouredynamic
assessment
of diurnal urinary
incontinence. Arch Dis Child 1987; 62: 128-31. 2 Quist ES, Kirstensen ES, Nielson KK, et al. Detrusor
instability in children with infection and enuresis. Urol Internat 1986; 41: 196-98. 3. Sorensen SS, Nielsen JB, Norgaard JP, Knudsen LM, Djurhuus JC. Changes in bladder volume with repetition of water cystometry. Urol Res 1984, 12: 205-08. 4. Hunter J (1856). Cited by Speakman MJ, Sethia KK, Fellows GJ, Smith JC. A study of the pathogenesis, urodynamic assessment and outcome of detrusor instability associated with bladder outflow obstruction. Br J Urol 1987; 59: 40-44 5. Lyon RP, Marshall S. Urinary tract infections and difficult urination in girls: Long-term follow-up. J Urol 1971; 105: 314-17. 6. Hendren WH. Postenor urethral valves in boys: a broad clinical spectrum J Urol 1971, 106: 298-307. 7. Mahony DT, Laferte RO. Studies of enuresis VII. Results of distal internal urethrotomy in girls with juvenile urinary incontinence. Urology 1974, 4: 162-72 8. Arnold SJ, Ginsburg A. Radiographic and photoendoscopic studies in posterior urethral valves in enuretic boys. Urology 1974, 4: 145-54. 9. Mundy AR. The unstable bladder. Urol Clin N Am 1985; 12: 317-28. 10. Palmtag H. The site of functional infravesical obstruction in children Bri J Urol 1983; 55: 395-401. recurrent urinary tract
EPIDERMAL CELLS IN CULTURE
SIR,-Dr Blair and colleagues (Aug 29, p 483) state that epithelial cell culture techniques (for preparing epidermal grafts) "present almost insurmountable difficulties in maintenance of sterility and prevention of fibroblast overgrowth". In this laboratory, grafts composed of epidermal cells have been grown in culture for the treatment of bums,’ leg ulcers, and congenital naevi. Other centres have also reported the successful use of cultured epithelium in the ofburns,2-s leg ulcers,6 junctional epidermolysis bullosa,7 split thickness skin graft donor sites.8 Under proper culture conditions, microbial contamination is very rare. It is the patient who is regularly contaminated, but that is a problem for the surgeon not the cell biologist. The presence of appreciable numbers of fibroblasts is unusual in 3T3-supported cultivation but can easily be controlled by selective detachment of the fibroblasts with edetic acid (EDTA).9 Far from being insurmountable, these problems are hardly worth mentioning if cultivation is properly carried out. The successful use of this technique throughout the world suggests a very promising future for its clinical use. treatment
and
BLADDER INSTABILITY OR URETHRAL CAUSES?
SiR,-Diurnal and nocturnal enuresis, urinary frequency, and urgency in children are often attributed to psychological causes, and your Aug 8 editorial (p 314) does well to draw attention to the fact
studies in such children bladder capacity, bladder trabeculation, reflux, and, most commonly, detrusor instability and a wide bladder neck. Unfortunately, you uncritically accept the diagnosis of "bladder instability" and underplay urethral causes for the problems discussed. A diagnosis of bladder instability relies upon cystometry, and cystometry is not always reliable or reproducible z3 Nor does it reveal urethral obstruction, sensation, or activity. As a test of lower urinary tract function or disease, therefore, it remains at best incomplete, at worst wholly misleading. The test merely reveals a sign, and it is a mistake to treat a sign as a disease. The ability of bladder events to produce the symptoms under discussion has been over-rated. Increased bladder pressure, bladder contractions, and bladder instability do not necessarily result in symptoms. The bladder cannot produce incontinence without urethral cooperation. Extensive and weighty evidence supports urethral disease as a cause of the voiding symptoms and organic findings reported. In 1856 John Hunter’ commented on the connection between urinary frequency, bladder trabeculation, and obstruction. Dilatation of fibrous distal urethral segment totally cured 88% of 104 girls suffering with non-infectious "... day wetting urgency and frequency".5 Such symptoms are almost always relieved by adequate urethral treatment.6-8 Obstruction remains the only proven cause of non-neuropathic instability.9 The "wide bladder
that urodynamic frequently reveal
and low
radiographic functional
Department of Physiology and Biophysics, Harvard Medical School, Boston, Massachusetts 02115, USA
TANIA PHILLIPS OLANIYI KEHINDE
NE, Mulliken JB, Banks-Schlegel S, Kehinde, O, Green H Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet 1981, i: 75-78. Pittelkow MR, Scott RE. New techniques for the in vitro culture of human skin keratinocytes and perspectives on their use for grafting of patients with extensive bums Mayo Clin Proc 1986; 61: 771-77. Hefton JM, Madden MR, Finkelstein JL, Shires GT. Grafting of burn patients with allografts of cultured epidermal cells Lancet 1983; ii. 428-30. Cuono C, Langdon R, McGuire J. Use of cultured epidermal autografts and dermal allografts as skin replacement after bum injury. Lancet 1986, i 1123-24 Teepe R, Ponec M, Kreis RW, Hermans RP Improved method for treatment of burns with autologous cultured human epithelium. Lancet 1986, i 385 Phillips T, Leigh IM, Hackett H, et al. Allografts of cultured keratinocytes m clinical
1. O’Connor
2.
3 4.
5 6.
Br J Dermatol 1986; 115: 21-22 Lin AN, Varghese MC, et al. Treatment of junctional epidermolysis bullosa with epidermal autografts. J Am Acad Dermatol 1987, 17: 246-50 8. Thivolet J, Faure M, Demiden A, Mauduit G. Long term survival and immunological tolerance of human epidermal allografts produced in culture. Transplantation 1986; practice.
7. Carter
DM,
47: 274-80. 9. Sun T-T, Green H. Differentiation of the epidermal keratinocyte formation of the cornified envelope Cell 1976, 9: 511-21.
in
cell culture