Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 73 records · Page 4Linked to original sources

PubMed1997

"Sandwich" preoperative and postoperative combined chemotherapy and radiation in tethered and fixed rectal cancer: impact of treatment intensity on local control and survival.

PURPOSE: The present "sandwich" preoperative and postoperative chemotherapy and radiation study was undertaken to evaluate the impact of treatment intensity on the local control and survival in tethered or fixed rectal adenocarcinoma (T3, 4 NX M0). METHODS AND MATERIALS: Between 1990 and 1992, 27 patients were treated with this sandwich protocol. Preoperative therapy consisted of 4 weeks of concurrent radiation (40 Gy) and chemotherapy (mitomycin C on day 1, 5-fluorouracil infusion and leucovorin on days 1-4 and days 15-18, respectively), and one cycle of bolus 5-fluorouracil and leucovorin chemotherapy. After surgery, they received 2 additional weeks of radiation (18 Gy) and 4 days of similar chemotherapy. The outcome was compared to another 54 patients who were treated with our previous preoperative chemoradiation protocol (mitomycin C, 5-fluorouracil infusion and 40 Gy of pelvic RT). RESULTS: The complete resectability rate was improved from 91% in the preoperative protocol to 100% in the sandwich protocol, and the pathologic complete response rate (T0 N0 M0) was increased from 4 to 15%. There was no local recurrence in the sandwich protocol. The 4-year local failure rate was 23 vs. 0% (p = 0.005). The 4-year distant failure rate was 47 vs. 28% (p = 0.079). The 2-year and 4-year survival were 63 and 41% for the preoperative protocol, vs. 92 and 72% for the sandwich protocol, respectively (p = 0.014). There were more treatment-related Grade 2 diarrhea, but not Grade 3/4 diarrhea in the sandwich protocol. Two patients (7%) in the sandwich protocol developed late gastrointestinal complications. CONCLUSIONS: More intensive radiation and chemotherapy appeared to improve the resectability, local control, and survival in tethered and fixed rectal cancers. There was a moderate but acceptable increase in the bowel morbidity.

Adenocarcinoma↗

PubMed1997

Mechanism of sustained E-selectin expression in cultured human dermal microvascular endothelial cells.

Persistent E-selectin expression has been proposed to be a unique property of dermal vascular endothelium that directs skin-specific homing of a subpopulation of circulating memory T cells. We compared the kinetics of E-selectin expression on cultured human dermal microvascular endothelial cells (HDMEC) with expression on HUVEC. Following treatment with TNF, E-selectin on HDMEC appears more slowly than on HUVEC (peak values 6-8 vs 4 h, respectively) and is sustained at significantly higher levels after 24 h. E-selectin mRNA, analyzed by S1 nuclease protection, consists of a single predominant transcript that follows a similarly transient time course in both cell types. Cell surface E-selectin is internalized more slowly on HDMEC than on HUVEC (t1/2 = 4.3 vs 1.6 h, respectively) as measured by serial FACS analyses in the presence of the protein synthesis inhibitor cycloheximide. In comparison, intercellular adhesion molecule-1 (ICAM-1) expression is not measurably reduced by either cell type under the same conditions. HDMEC are similar to HUVEC in rates of pinocytosis or receptor-mediated endocytosis. Pulse-chase analysis indicated that the degradative half-life of E-selectin protein is greater in HDMEC than in HUVEC (1.9 vs 1.5 h, respectively). E-selectin internalization in microvascular endothelial cells (EC) from lung and subcutaneous fat is slow, like HDMEC, whereas internalization in large vessel EC from saphenous vein and aorta is rapid, like HUVEC. We conclude that HDMEC sustain higher levels of expression at 24 h by slower internalization and degradation of E-selectin protein and that this may be a general property of microvascular EC.

Adult↗

PubMed1997

Noradrenergic and serotonergic function in posttraumatic stress disorder.

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Adult↗

PubMed1997

Induction of mouse cytochrome P450 2B enzymes by amine metabolites of musk xylene: contribution of microsomal enzyme induction to the hepatocarcinogenicity of musk xylene.

Musk xylene (MX) is a synthetic nitromusk perfume ingredient that, although uniformly negative in genotoxicity testing, causes liver tumors in B6C3F1 mice. MX is also capable of inducing cytochrome P450 enzymes in a manner similar to that of phenobarbital (PB), which suggests that epigenetic mechanisms may be involved in the carcinogenic response. At the same time, MX is metabolized in vivo by nitroreduction, a reaction catalyzed by intestinal flora that yields aromatic amine metabolites. These amine metabolites are also capable of inactivating CYP2B10, the major cytochrome P450 enzyme induced by MX treatment. In the study reported here, the monoamine metabolites of MX, o- and p-NH2-MX, were evaluated for their potential to induce CYP2B10 and CYP1A2 mRNAs. Northern blot analyses indicated that both amines markedly induced CYP2B10 mRNA, whereas CYP1A2 mRNA, the enzyme implicated in the bioactivation of aromatic amines and frequently induced by aromatic amines, was induced only slightly, a response that was not different from that seen with PB. Induction of CYP2B10 mRNA suggested that the amine metabolites may contribute to the enzyme induction profile seen with MX treatment. To test this hypothesis, mice were treated with broad-spectrum antibiotics (neomycin, tetracycline, and bacitracin) to eliminate the intestinal flora and prevent formation of o- and p-NH2-MX. In antibiotic-treated mice treated with MX (200 mg/kg) for 4 d, no evidence of microsomal enzyme induction was observed, including no increases in liver weight, total cytochrome P450 content, or CYP2B protein levels. These results indicate that the amine metabolites of MX are responsible for the enzyme induction seen after MX administration. Thus, the biochemical and molecular effects of amine metabolites of MX are markedly different from those of other aromatic amines but very similar to those of PB. Therefore, it appears that MX is a non-genotoxic chemical that may cause mouse liver tumors in a manner analogous to that of PB.

Amines↗

PubMed1997

Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene.

Musk xylene (MX) (1,3,5-trinitro-2-t-butylxylene) is a nitromusk perfume ingredient that although uniformly negative in a battery of genotoxicity tests, produces a high incidence of liver tumors in mice. The purpose of this work was to characterize the profile and dose-response relationship of microsomal enzyme induction following exposure to MX. MX was dosed by gavage to male B6C3F1 mice for 7 days at 0, 1, 5, 10, 20, 50, 100, and 200 mg/kg after which microsomes were prepared. At 200 mg/kg, MX increased liver weight by about 65% and increased microsomal cytochrome P-450 content 2-fold over control. MX increased microsomal activity for O-dealkylation of 7-ethoxy and 7-methoxyresorufin 4- and 2-fold, respectively, and increased the N-demethylation of erythromycin approximately 2-fold. These results were generally consistent with increased CYP1A1, 1A2, and 3A protein levels determined by Western blotting. In contrast, whereas no increase in O-dealkylation of 7-pentoxyresorufin (PROD) was observed, MX treatment increased CYP2B protein levels about 25-fold over control at 200 mg/kg. Furthermore, a single dosage of MX (200 mg/kg) increased Cyp2b-10 mRNA to a maximal level and with a time course similar to phenobarbital (PB). To study inhibition of CYP2B enzymes in vivo, mice were treated with PB (0.05% in drinking water for 5 days), then given a single dosage of corn oil or MX (200 mg/kg) at 2 or 18 hr before necropsy. PB treatment increased PROD activity 25-fold, and at 2 hr after MX treatment (associated with peak plasma levels of MX), there was no change in the PB-induced PROD activity. However, at 18 hr, MX treatment decreased PROD activity by 90%. Despite the in vivo inhibition, in vitro studies indicated that MX did not cause mechanism-based inactivation of CYP2B enzymes. The potential for nitroreduction of MX (catalyzed by anaerobic intestinal bacteria) to contribute to the inhibition of CYP2B enzyme activity was evaluated in a separate group of PB-induced mice that were dosed orally with a regimen of broad spectrum antibiotics (neomycin, tetracyline, and bacitracin) to reduce gut flora prior to administration of MX. In these animals, MX (200 mg/kg) did not inhibit PB-induced PROD activity. In summary, MX treatment produced general hepatic changes consistent with induction of CYP2B enzymes in mice and caused a large increase in CYP2B protein and mRNA levels. These data indicate that MX is a PB-like inducer of cytochrome P-450 enzymes and may cause liver tumors in a manner analogous to PB. However, no increase in CYP2B enzyme activity was observed, suggesting that MX or metabolites of MX also inhibit this enzyme. When the intestinal flora was eliminated by antibiotic treatment, MX no longer inhibited the CYP2B enzyme, indicating that anaerobic bacteria are capable of metabolizing MX, and suggesting that amine metabolites formed by nitroreduction are involved in the inhibition of mouse CYP2B enzymes.

Administration, Oral↗

PubMed1997

Macular pattern retinal dystrophy, adult-onset diabetes, and deafness: a family study of A3243G mitochondrial heteroplasmy.

PURPOSE: To correlate mitochondrial DNA (mtDNA) mutation with phenotypic expression in three members of a Finnish family with macroreticular pattern dystrophy, non-insulin-dependent diabetes mellitus, and deafness. METHODS: A multiplex polymerase chain reaction/allele-specific oligonucleotide method was used to screen 10 mtDNA point mutations known to cause mitochondrial DNA disorders, often characterized by myopathy, retinopathy, or both. Quantitative analysis of mutant mitochondrial DNA was performed in three tissue types in each of three family members by determining the percentage of mutant mtDNA in blood, buccal cells, and hair follicles. RESULTS: A heteroplasmic A3243G mtDNA point mutation was found in each of the three family members studied. Heteroplasmy refers to the coexistence of normal and mutant mitochondria in the same cell. The average percentage of mutant heteroplasmy ranged from 11% to 25%. The severity of disease symptoms did not appear to correlate with the average degree of mutant heteroplasmy in the three tissues analyzed. CONCLUSIONS: Molecular confirmation in this family emphasizes the importance of mitochondrial DNA mutation analysis in patients with macular pattern retinal dystrophy and other mitochondrial associated nonocular disease, such as non-insulin-dependent diabetes mellitus and deafness. The detection of a disease-associated mitochondrial DNA mutation warrants genetic counseling, appropriate patient follow-up, and possibly the molecular testing of other at-risk family members.

Age of Onset↗

PubMed1997

Women's perception of pain and distress during intravenous catheterization and urethral mini-catheterization.

A study was done to prospectively compare the pain and distress of urethral mini-catheterization (MC) with the pain and distress of intravenous (IV) catheterization in women. Ten-centimeter visual analog scales were used on which the left end represented "no pain" or "no distress" and the right "the worst pain imaginable" or "extreme distress." Distress was defined to include embarrassment, anxiety, or fear. A convenience sample of 40 adult women who presented to a university emergency department and were undergoing both procedures as part of their management appraised pain and distress after IV placement and urethral MC. The mean IV pain score was 4.2 cm, whereas the mean MC score was only 2.6 cm (P = .02). The IV and MC distress score means were similar (2.3 v 2.6 cm, P = .55). These results suggest that patients perceive urethral MC as less painful than IV placement. The distress scores of these two procedures did not differ and were low in both instances.

Adolescent↗

PubMed1997

The impact of the homecoming reception on the development of posttraumatic stress disorder. The West Haven Homecoming Stress Scale (WHHSS).

This study reports on the development of a self-report measure of the homecoming experience among Vietnam veterans with posttraumatic stress disorder (PTSD). The West Haven Homecoming Stress Scale (WHHSS), measuring Frequency of Events, Intensity of Feelings, and Level of Support during the first 6 months after return from overseas, and within the past 6 months, was collected from 247 veterans who were receiving inpatient treatment for PTSD. Homecoming Stress was the most significant predictor of current PTSD symptomatology superseding combat exposure, childhood and civilian traumas, and stressful life events. A factor analysis resulted in four orthogonal factors: Shame, Negative Interpersonal Interaction, Social Withdrawal, and Resentment. Homecoming Stress was unchanged over the course of a 4 month inpatient program.

Adult↗

PubMed1997

Single session effects of treatment components within a specialized inpatient posttraumatic stress disorder program.

This study examined the potential contributions of individual treatment components within one inpatient posttraumatic stress disorders (PTSD) program. Fifteen treatment components were assessed by a self-report instrument administered to a cohort of veterans just before and immediately after each session approximately halfway through the program. Components with an external focus, action modality, and, secondarily, little Vietnam content were associated with more improvement than components with an internal focus, verbal modality, or high Vietnam content. Improvement was greatest in veterans with fewer PTSD symptoms. Short-term improvement was not correlated with veterans' ratings at discharge of component effectiveness. These results were later confirmed on a second cohort. This study supports the potential roles of distraction and physical release, as opposed to exploratory verbal discussion, in the treatment of chronic combat-related PTSD.

Adult↗

PubMed1997

Assessing the structure, content, and perceived social climate of residential posttraumatic stress disorder treatment programs.

This study utilized a comprehensive assessment of program structure, content, and social climate to determine whether specialized residential posttraumatic stress disorder (PTSD) programs (SIPUs, n = 19) can be differentiated from general psychiatric units (GPUs, n = 18) within the Department of Veterans Affairs. Significant differences between program types were found: SIPUs were more clearly differentiated from the larger hospital system, had more strict patient selection criteria and program regulations, longer length of stays and lower admission rates, and spent more program time on PTSD symptoms and war zone experiences than GPUs. Veterans in the SIPUs (n = 453) rated the programs significantly higher on most social climate measures than veterans with PTSD in the GPUs (n = 153), indicating that veterans perceived these programs as more active, supportive, and better structured.

Adult↗

PubMed1997

Treatment preferences of Vietnam veterans with posttraumatic stress disorder.

This study attempted to examine patterns over time in treatment preferences of 65 veterans who completed a 4 month inpatient posttraumatic stress disorders (PTSD) program in order to reveal potentially more beneficial types of treatment. Veterans rated the severity of their symptoms and degree of benefit of 35 different treatment components at discharge, and at 4 and 12 months follow-up. Veterans rated their symptoms as having not changed at discharge, and worsening by 4 months. Veterans initially perceived components that were high in Vietnam content, exploratory in purpose, verbal in modality, and personally focused as most effective, but by 12-month follow-up they perceived these as less effective than components that were low in Vietnam content, educative, action oriented, and externally focused. These effects were strongest among veterans with higher levels of PTSD symptomatology. Combat exposure, childhood abuse, and race were generally not significant predictors of response. These results underscore the importance of further inquiry into the relative value of rehabilitative-oriented and psychotherapeutic-oriented treatments for veterans with severe and chronic PTSD.

Adult↗

PubMed1997

Effect of mycophenolic acid on TNF alpha-induced expression of cell adhesion molecules in human venous endothelial cells in vitro.

1. Mycophenolic acid (MPA) is an inhibitor of inosine-5'-monophosphate dehydrogenase and therefore interferes with cellular GTP biosynthesis. Recently, MPA has been used as an antiproliferative and immunosuppressive agent. In the present study, the effect of MPA on the expression of the endothelial cell adhesion molecules (CAMs), intercellular (I) CAM-1, vascular (V) CAM-1 and endothelial (E)-selectin, was investigated in tumour necrosis factor-alpha (TNF alpha)-activated cultured human venous endothelial cells (EC). 2. Surface expression of CAMs was measured by flow cytometry and mRNA expression by Northern blot analysis. Transcriptional activation of CAMs by the nuclear factor NF-kappaB was determined by an electromobility shift assay. The function of CAMs was studied by a static adhesion assay with human monocyte-like undifferentiated U937 cells. 3. Pretreatment of TNF alpha- (5 ng ml(-1), 12 h) activated EC with MPA (10 microM, 24 h) increased the binding of U937 cells, which had not been treated with MPA, by approximately 2 fold. MPA-pretreatment of EC did not affect TNF alpha-induced surface expression of ICAM-1. However, VCAM-1 and E-selectin were increased 2-3 fold and remained elevated up to 24 h, by which time TNF alpha-activated control EC had returned to baseline levels of expression. The effect of MPA on the surface expression of CAMs was half-maximal at approximately 1 microM and required > or = 12 h of pretreatment. Guanosine (0.3 mM), a precursor of GTP, did not prevent the effect of MPA on the expression of CAMs in TNF alpha-activated EC. 4. Kinetics of mRNA expression of CAMs mirrored protein expression: mRNA for ICAM-1 was unaffected, whereas TNF alpha-induced mRNA expression for E-selectin and VCAM-1 was prolonged and increased by MPA. This effect was not due to increased transcription mediated by the nuclear transcription factor NF-kappaB. However, half-life for E-selectin mRNA was increased 10 fold by MPA, whereas ICAM-1 mRNA half-life was unchanged. 5. The data demonstrate that apart from its antiproliferative effects on lymphocytes, MPA enhances TNF alpha-induced VCAM-1 and E-selectin surface expression on EC by selectively increasing the mRNA-stability of these cell adhesion molecules. This effect of MPA on EC appears to be independent from inhibition of inosine-5'-monophosphate dehydrogenase.

Antibiotics, Antineoplastic↗

PubMed1997

Adaptation in the vertebral column: a comparative study of patterns of metameric variation in mice and men.

In this paper we examine metamerism in the vertebral column of certain mammals from the perspectives of development and adaptation. To this end we examine the patterns of metameric variation of dimensions of the neural (vertebral) canal, vertebral body and spinous process in man and inbred strains of mice. The data from inbred strains of mice indicate that variability in dimensions within a strain reflects the temporal ordering and nature of developmental influences on vertebral morphogenesis. Differences between strains parallel the within-strain findings. These findings are attributed to somatic and neural influences on morphogenesis. Comparisons between mice and man indicate that these same influences can be invoked to explain and interpret the mosaic nature of vertebral column evolution. These findings lead us to conclude that different vertebral elements and levels are subject to different interactions of evolutionary and morphogenetic influences. The study of these influences and their interactions should prove fruitful in developing an understanding of the relationship between adaptation, development, growth and function in the skeleton generally.

Adaptation, Physiological↗

PubMed1997

An existential model of group therapy for chronic mental conditions.

A group therapy model for chronic mental patients based on existential principles is described. Focusing on the existential dilemmas of chronically ill patients accesses their inner life and acknowledges their immense strengths in tolerating the illness. These effects can improve the patients' motivation for and compliance with treatment and lower distressing secondary conditions such as shame, hopelessness, and suicidality. The model uses the methods of (a) linking, (b) differentiating the therapy team, and (c) addressing the core issues to counteract the negative processes of derealization, powerlessness and irrelevance that hinder group therapy with these patients. Therapists attempt to highlight divergent perspectives of irresolvable dilemmas, offering patients the opportunity to experience and to communicate the courage, tolerance and love required to carry the burden of chronic mental illness.

Adult↗

PubMed1997

Interactive psychoeducational group therapy for traumatized women.

A specialized form of outpatient group therapy with traumatized women is described. Interactive psychoeducational group therapy (IPGT) aims to help the survivor differentiate her self-representations from traumatic schemata that she may have assimilated since the traumatic event. Such assimilation is viewed as leading to a number of negative effects, including shame, social isolation, distorted body image, and sense of meaninglessness. Using a membership with heterogeneous trauma, cognitive-distancing techniques, corrective interpersonal enactments, and specifically designed ceremonies, IPGT attempts to encourage survivors to alter their relationship to the traumatic event and the illness of posttraumatic stress disorder. Clinical examples demonstrate members' improvement in self-image, interpersonal relationships, and sense of belonging to the community at large.

Adult↗

PubMed1997

Toward parsimony in the inpatient community meeting on a short-term unit.

The role of the community meeting on the inpatient psychiatric unit has been continuously transformed by the radical shifts in the practice of inpatient psychiatry over the past 40 years. The current clinical climate of extremely shortened lengths of stay requires the community meeting to directly address the inpatient unit's primary tasks of stabilization, discharge planning, and treatment compliance and to avoid the regressive effects of large, unstructured groups. In these conditions, an interpretive model of the community meeting, which addresses patients' projections onto staff behavior, seems problematic and not widely applicable because it turns patients' attention away from the adaptational challenges they face from their external social environments. It also places heavy demands on staff time, training, and tolerance.

Adaptation, Psychological↗

PubMed1997

Mechanism-based inactivation of mouse hepatic cytochrome P4502B enzymes by amine metabolites of musk xylene.

Musk xylene (2,4,6-trinitro-1-t-butylxylene; MX) is a synthetic nitromusk perfume ingredient that induces and inhibits mouse cytochrome P4502B (CYP2B) enzymes in vivo. The purpose of the present work was to determine whether amine metabolites of MX contributed to the enzyme inhibition and, if so, to define the nature and kinetics of this inhibition. When dosed orally to phenobarbital (PB)-treated mice, MX (200 mg/kg) inhibited > 90% of the PB-induced O-dealkylation of 7-pentoxyresorufin (PROD), and [14C]MX equivalents bound covalently to microsomal proteins. However, when this experiment was repeated in mice pretreated with antibiotics to eliminate the gastrointestinal flora, no decrease in PB-induced PROD activity and no covalent binding to microsomal proteins were observed. Thus, the ability of antibiotic treatment to eliminate the enzyme inhibition and covalent binding implicated amine metabolites of MX formed by nitroreduction in anaerobic intestinal flora as obligatory for these effects. Two monoamine metabolites of MX were synthesized to study enzyme inhibition directly. These metabolites were 2-amino-4,6-dinitro-1-t-butyl-xylene and 4-amino-2,6-dinitro-1-t-butylxylene, referred to as o-NH2-MX and p-NH2-MX, respectively, reflecting the position of the amine substitution relative to the t-butyl function. In the in vitro studies with PB-induced mouse liver microsomes, both amines inhibited PROD activity when preincubated in the absence of NADPH. However, only p-NH2-MX caused a time- and NADPH-dependent loss of PROD activity, and the inactivation rate was a pseudo-first-order process that displayed saturation kinetics. These results indicate that p-NH2-MX is a mechanism-based inactivator of mouse CYP2B enzymes. From kinetic analyses, the Ki was calculated to be 10.5 microM and the Kinact was 1.2 min-1. As final confirmation of the inhibitory effects of p-NH2-MX on mouse CYP2B enzymes, the amine (0.67 mmol/kg) was dosed orally to PB-induced mice. At 2 hr after dosing, p-NH2-MX inhibited essentially all of the PB-induced PROD activity, whereas an equimolar dosage of parent MX had no effect at this early time. Thus, although MX is an inducer of mouse CYP2B enzymes, an amine metabolite of MX is a mechanism-based inactivator of mouse CYP2B10. Furthermore, it is likely that the amine is responsible for the lack of functional CYP2B enzyme activity associated with induction of this enzyme by MX.

Animals↗

PubMed1997

Experimental model of pudendal nerve innervation of a skeletal muscle neosphincter for faecal incontinence.

BACKGROUND: Faecal incontinence is difficult to treat. A variety of reconstructive procedures has been described, but none is entirely satisfactory. This study evaluated the feasibility of cross-innervating a skeletal muscle neosphincter with the pudendal nerve in a canine model. METHODS: Thirty dogs were rendered surgically incontinent (the pudendal nerve was cut and the external sphincter was partially excised). A neosphincter was then created using the semitendinosus muscle. In ten dogs pudendal nerve transposition (PNT) to the nerve to the semitendinosus muscle was performed. Ten dogs were given a dynamic neosphincter by inserting a pulse generator at 6 weeks. The remaining ten dogs served as controls with passive semitendinosus wraps. Anal manometry was performed before operation and monthly for 5 months. Muscle biopsies, performed at the initial operation and at 5 months, were stained for slow- and fast-twitch fibres, and were examined histologically. RESULTS: At 1 month, mean sphincter function was 32 per cent of the preoperative value in the control animals, 34 per cent in the PNT group and 27 per cent in the electrostimulation group; all dogs were incontinent. At 5 months the mean recovery of sphincter function was 42 per cent of the preoperative value in controls, 100 per cent in dogs with PNT (P < 0.001) and 63 per cent in dogs having electrostimulation (stimulator on) (P = 0.02). Six dogs with PNT had squeeze pressures equal to or greater than preoperative levels. At 5 months the ratio of slow to fast fibres was significantly greater in all dogs (control P = 0.01, PNT P < 0.005, electrostimulation P < 0.001). CONCLUSION: Use of the pudendal nerve to innervate a canine skeletal muscle anal wrap produced a functional anal sphincter that was superior to electrically stimulated and passive wraps.

Anal Canal↗