Pathogenesis of obliterative bronchiolitis. Possible roles of platelet-derived growth factor and basic fibroblast growth factor.
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Animals↗
Biomedical subjects
J J Murray
Publications and source records attributed to J J Murray.
Anal fissure in Crohn's disease: a plea for aggressive management.
PURPOSE: This study was undertaken to identify clinical characteristics, natural history, and results of medical and surgical treatment of anal fissures in Crohn's disease. METHODS: This is a retrospective review of patients with Crohn's disease and anal fissure. RESULTS: Of the 56 study patients, 49 (84 percent) had symptomatic fissures. Fissures were most commonly (66 percent) located in the posterior midline, and 18 patients (32 percent) had multiple fissures. Fissures healed in one-half of patients treated medically. Factors predictive of successful medical treatment included male gender, painless fissure, and acute fissure. Of 15 patients, 10 (67 percent) treated surgically healed. Fissures in seven of eight patients (88 percent) who underwent anorectal procedures healed compared with fissures in only three of seven patients (43 percent) who underwent proximal intestinal resection. In the group of 50 patients with complete follow-up studies, an anal abscess or fistula from the base of an unhealed fissure developed in 13 patients (26 percent). More fissures healed after anorectal surgery (88 percent) than after medical treatment alone (49 percent; P = 0.05) or after abnormal surgery (29 percent; P = 0.03). CONCLUSION: This series documents that unhealed fissures frequently progress to more ominous anal pathologic disease. Judicious use of internal sphincterotomy appears to be safe for fissures unresponsive to medical treatment.
Adolescent↗
Latency measurement of rectoanal reflexes.
PURPOSE: Latency values of rectoanal reflexes may be altered in disorders of the pelvic floor. Evaluation of this relatively uninvestigated aspect of rectoanal reflexes may have diagnostic implications in patients with disorders of defecation. METHODS: We studied the latency of rectoanal inhibitory and excitatory reflexes to sequential balloon distention of the rectum with 60 ml and 120 ml of air in 14 normal controls (mean age, 41.5 (range, 19-66) years), in 14 patients with fecal incontinence (FI) (mean age, 44.2 (range, 28-72) years), and in 14 patients with slow transit constipation (STC) (mean age, 40.6 (range 22-68) years). RESULTS: The mean latency of inhibition (FI = 5.3 seconds; STC = 4.6 seconds; controls = 5.1 seconds) was remarkably similar for the three groups (P = 0.19). The mean latency of excitation in the proximal anal canal (FI = 2.8 seconds; STC = 2.5 seconds; controls = 2.8 seconds) was comparable in the three groups (P = 0.58). The mean latency of excitation in the distal anal canal (FI = 4.8 seconds; STC = 2.6 seconds; controls = 2.7 seconds) was prolonged in patients who were incontinent compared with the other two groups (P < 0.01). CONCLUSIONS: Proximal rectoanal excitation and inhibitory reflexes, when present, have a constant latency, irrespective of the underlying condition. The different latency values for proximal and distal rectoanal excitatory reflexes in patients with FI may indicate disparate denervation damage to the external anal sphincter.
Adult↗
Distal rectoanal excitatory reflex: a reliable index of pudendal neuropathy?
PURPOSE: Denervation of the extrinsic anal sphincter and pudendal neuropathy are confirmed by electrophysiologic or electromyographic testing, techniques that may not be available universally and require special equipment and training. A simple manometric test that is easy to perform and complements existing studies was performed to confirm pudendal neuropathy. METHODS: Fourteen patients with excessive defecatory straining and 30 patients with idiopathic fecal incontinence were studied by electrophysiology and balloon reflex manometry. Pudendal nerve terminal motor latency (PNTML) and rectoanal excitatory reflex were evaluated for abnormalities. Results were compared with 20 controls who had no anorectal complaints and who had similar testing performed. RESULTS: In controls, PNTML was normal in all but one person. Rectoanal excitatory reflex could be elicited in all controls with either 20 or 40 ml of air. Four different types of balloon reflex responses were observed in patient groups: diminutive excitation, delayed excitation, excitation at high volume of distention only, and absent excitation. Ten patients with fecal incontinence had normal PNTML but abnormal distal excitatory reflex, 5 patients had abnormal PNTML but normal distal excitatory reflex, and 15 patients had both PNTML and excitatory reflex that were abnormal. In patients with excessive defecatory straining, results of both tests were abnormal in six patients, and eight patients had abnormal excitatory reflex but normal PNTML. CONCLUSION: Pudendal neuropathy may result in abnormalities of excitatory reflex morphology or other characteristics. Abnormal distal excitatory reflex may complement electrophysiologic findings or may serve as a suitable alternative to confirm pudendal neuropathy in centers where facilities for formal testing are not available.
Adult↗
Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors of subsequent pouch salvage.
PURPOSE: The aim of this study was to understand better the cause and predictability of pouch failure requiring rediversion after ileal pouch-anal anastomosis and to assess the ultimate outcome of patients in a large ileal pouch series who required rediversion. METHODS: Data from 460 patients completing ileal pouch-anal anastomosis at one institution were recorded from both a prospectively accumulated ileal pouch registry and patient medical records. RESULTS: Of 460 patients, 21 (4.6 percent) who underwent ileal pouch-anal anastomosis required rediversion. Five of these patients subsequently had successful restoration of pouch continuity, leaving a permanent failure rate of 16 of 460 patients (3.5 percent). The most common reasons for rediversion were pouch fistula formation (12) and poor functional results (5). Preoperative factors, including age, previous colectomy, and indication for colectomy, did not predict eventual need for rediversion. Patients requiring rediversion had significantly higher rates of postoperative complications (95 vs. 43 percent; P < 0.001). Specifically, this group had a higher rate of postoperative pouch fistula (57 vs. 3.4 percent; P < 0.001). Additionally, a final diagnosis of Crohn's disease significantly predicted the need for rediversion. Permanent pouch failure occurred in 36.8 percent of patients with a final diagnosis of Crohn's disease compared with 1.4 percent of patients with a final diagnosis of ulcerative colitis (P < 0.001). All five salvaged patients had fistula formation in the absence of Crohn's disease. CONCLUSIONS: The overall rate of permanent pouch failure is low. The majority of failures were related to fistula formation associated with Crohn's disease or poor functional results. Pouches complicated by fistulas not associated with Crohn's disease can be salvaged with temporary rediversion.
Adenomatous Polyposis Coli↗
Relationship between manometric anal waves and fecal incontinence.
PURPOSE: The significance of manometric anal waves is uncertain, and their fate and diagnostic importance are unknown. It is conceivable that in neurogenic fecal incontinence (NFI) the frequency and amplitude of these waves may be altered into specific, recognizable patterns. Evaluation of this unexplored relationship between fecal incontinence and anal manometric waves has potential diagnostic use. METHODS: Anal motility was studied in 20 patients, each with NFI and traumatic fecal incontinence (TFI), and results were compared with findings in 20 control subjects to determine changes in frequency and amplitude of anal waves in fecal incontinence. RESULTS: Frequency of slow waves when present (NFI = 9.5/minute; TFI = 9.5/minute; control subjects = 9.1/minute) was identical in the three groups (P > 0.05). Amplitude of slow waves (NFI = mean, 4.3 mmHg; TFI = mean, 3.9 mmHg; control subjects = mean, 6.6 mmHg) was reduced in patients who were incontinent compared with control subjects but failed to reach statistical significance (P > 0.05). Frequency of ultraslow waves when present (NFI = mean, 0.75/minute; TFI = mean, 0.6/minute; control subjects = mean, 1.2/minute) was not statistically different between the three groups (P > 0.05). Amplitude of ultraslow waves (NFI = mean, 10.5 mmHg; TFI = mean, 23.4 mmHg; control subjects = mean, 29.6 mmHg) was significantly reduced in NFI vs. control subjects (P < 0.01) and between TFI vs. control subjects (P < 0.05). CONCLUSIONS: Manometric slow and ultraslow waves, when present, retain their frequency characteristics, irrespective of underlying disease. Amplitude of slow waves was not statistically different from control subjects, but the amplitude of ultraslow waves was significantly decreased in patients who were incontinent.
Adult↗
Rectal mucosectomy in the treatment of giant rectal villous tumors.
PURPOSE: Rectal mucosectomy, a technique adapted from restorative proctocolectomy, has been used to treat large rectal villous tumors. We compared morbidity, tumor control, and functional outcome following rectal mucosectomy with the results of more conventional transanal excision and piecemeal snaring and fulguration in patients with large rectal villous tumors. METHODS: We retrospectively reviewed the charts of inpatients who had undergone transanal surgery for villous tumors. RESULTS: Between 1983 and 1993, rectal mucosectomy, transanal excision, and snaring and fulguration were performed, respectively, in 12, 26, and 23 patients with large rectal villous tumors. Tumors treated by rectal mucosectomy had a larger mean diameter (8.5 cm) than those treated by transanal excision or snaring and fulguration (4.5 cm and 4.2 cm, respectively; P < 0.0001, analysis of variance). After a mean follow-up of 47 months, incidence of tumor persistence was 17 percent following rectal mucosectomy, 20 percent following transanal excision, and 40 percent following snaring and fulguration (P = 0.04, chi-squared). Tumor recurrence was 8 percent after rectal mucosectomy compared with 36 and 44 percent, respectively, after transanal excision (P = 0.09, chi-squared) and snaring and fulguration (P = 0.04, chi-squared). Clinically significant postoperative bleeding did not occur after rectal mucosectomy; 17 percent of patients had persistent mild incontinence. CONCLUSIONS: Rectal mucosectomy for villous tumors, a new application of an established technique, is safe and associated with low rates of tumor persistence and recurrence. Rectal mucosectomy may result in mild incontinence and should be reserved for large or circumferential lesions. For smaller lesions, transanal excision results are more reliable tumor eradication than snaring and fulguration.
Adenoma, Villous↗
Can manometric parameters predict response to biofeedback therapy in fecal incontinence?
PURPOSE: Biofeedback therapy may improve fecal control in up to 50 percent to 92 percent of patients with fecal incontinence. Identification of favorable manometric parameters before biofeedback therapy may help in selection of patients suitable for such therapy. METHODS: Twenty-eight patients with fecal incontinence (idiopathic, 11; iatrogenic trauma, 8; obstetric trauma, 9) who underwent biofeedback therapy were studied to determine whether manometric parameters could predict the result of therapy. Biofeedback was given using a computer software program designed to strengthen the external anal sphincter with auditory and visual feedback. RESULTS: Thirteen patients (46.4 percent) achieved excellent results; eight patients (28.6 percent) had good results, but seven patients (24.5 percent) failed to improve after biofeedback therapy. Resting or squeeze anal canal pressure, pressure volume, sphincter length, sphincter fatigue rate, and cross-sectional asymmetry of the entire sphincter before biofeedback failed to reveal any statistically significant differences between responders and nonresponders. However, the cross-sectional asymmetry of the high-pressure zone within the sphincter at rest was greater in nonresponders than in responders (not improved, 25.8 percent; good result, 20.2 percent; excellent result, 15.4 percent; P < 0.07). This difference was even greater on squeeze (not improved, 21 percent; good result, 17.6 percent; excellent result, 13.2 percent; P < 0.04). The number of biofeedback sessions, response on bearing down, and quality of rectoanal excitatory reflex were not reliable indicators of outcome. No statistical difference was found in mean resting and squeeze pressures after biofeedback between responders and non-responders. CONCLUSIONS: Except for increased cross-sectional asymmetry in the high-pressure zone, which may be a forerunner of adverse outcome, manometric parameters before biofeedback do not predict response to biofeedback therapy. Improvement in continence may be independent of resting and squeeze pressures achieved after biofeedback therapy.
Adult↗
State of the defunctionalized sphincter in patients undergoing ileoanal pouch anastomosis.
PURPOSE: Our aim was to determine manometric status and functional outcome of the ileoanal pouch procedure in a subset of patients with defunctionalized anal sphincters as a result of long-term fecal diversion. METHODS: The anal manometric profiles of 12 patients defunctionalized for one year or more were compared with 26 patients with nondefunctionalized anal sphincters. Functional data were obtained from the Lahey Clinic Ileoanal Pouch Registry. RESULTS: Preoperative manometric data revealed a mean resting pressure of 91.5 mmHg in the nondefunctionalized group vs. 68.7 mmHg in the defunctionalized group; mean squeezing pressure was 171.7 mmHg (nondefunctionalized group) vs. 102.3 mmHg (defunctionalized group); and squeezing pressure volume was 1,283,000 mmHg3 (nondefunctionalized group) vs. 585,000 mmHg3 (defunctionalized group). Functionally both groups had a mean of 6.1 bowel movements in a 24-hour period and could defer defecation for a mean of 2 hours. Leakage occurred in 22 percent of the defunctionalized group and 17 percent of the nondefunctionalized group (P = 0.35). CONCLUSION: Despite physiologic perturbations, the long-term, defunctionalized anal sphincter can adequately support a restorative procedure without regard to timing of pouch creation.
Adenomatous Polyposis Coli↗
bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas.
The bcl-2 gene is an oncogene that inhibits programmed cell death (apoptosis). We investigated by immunocytochemistry bcl-2 expression in normal colonic mucosa, hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. The purpose of the investigation was twofold; to assess the possible role of bcl-2 in colorectal tumorigenesis and to evaluate its clinical significance. The cases studied included 24 hyperplastic polyps, 49 adenomas, and 205 colorectal carcinomas. In both normal mucosa and hyperplastic polyps bcl-2 immunoreactivity was detected only in the proliferative cells of the colonic crypts. Conversely, bcl-2 immunoreactivity was noted in all adenomas irrespective of the degree of dysplastic change; it was diffuse in 84% of adenomas and focal in the remaining cases. In colorectal carcinomas bcl-2 expression was undetectable in 50% and focal (less than 50% immunostained neoplastic cells) in 38% of tumors. The remaining 12% of the carcinomas displayed diffuse (more than 50% immunostained neoplastic cells) bcl-2 immunoreactivity. In colorectal carcinomas bcl-2 expression was not correlated with relevant clinicopathologic parameters, including disease stage, tumor location and growth fraction, DNA ploidy, and p53 protein accumulation, and had no prognostic significance by univariate or multivariate analysis. These results suggest that bcl-2 oncoprotein may play a role in colorectal tumorigenesis, probably in the early phases of the adenoma-carcinoma sequence. bcl-2 expression in established tumors has no prognostic significance.
Adenocarcinoma↗
Insights into IgE-mediated lung inflammation derived from a study employing a 5-lipoxygenase inhibitor.
We have recently reported that the 5-lipoxygenase (5-LO) inhibitor, zileuton, alters lung inflammation produced by segmental antigen challenge in ragweed-allergic human subjects. Specifically, zileuton inhibited the urinary excretion of leukotriene E4 produced by antigen challenge, and the significant increase in bronchoalveolar lavage (BAL) eosinophils observed in subjects on placebo was not seen in subjects on zileuton. In this manuscript, we report additional data obtained during that study which provide information about mechanisms important during IgE-mediated inflammatory reactions in the lung. Three different areas are addressed: 1) the time to recovery of the lung from an IgE-mediated inflammatory response; 2) mechanisms related to the generation of cyclooxygenase products in the lung after antigen challenge and the effect of 5-LO inhibition on the production of cyclooxygenase metabolites; and 3) mechanisms responsible for the production of peptide leukotrienes in the lung and lung injury (as shown by albumin influx into the alveolar air space) 24 h after antigen challenge. We observed the following: 1) a significant BAL eosinophilia and basophilia remained 31 days (range 21-48) after segmental antigen challenge and bronchoalveolar lavage; 2) a decreased quantity of BAL cyclooxygenase products, as well as lipoxygenase products, in the presence of 5-LO inhibition; and 3) correlative analyses which suggest that while eosinophils appear most important for the production of peptide leukotrienes and lung injury 24 h after antigen challenge in subjects taking placebo, other effector mechanisms, perhaps those involving basophils and the initial mast cell triggering event, appear to gain in importance when the IgE-mediated inflammatory reaction is blunted by 5-LO inhibition.
Anti-Inflammatory Agents, Non-Steroidal↗
Fluosol in myocardial reperfusion injury.
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Animals↗
Methodological issues involved in sampling a population of the elderly for a dental survey.
A random sample of adults over 60 years of age was drawn from three different areas of England to take part in a survey of their dental status and needs. The paper describes sampling methods and operational problems in trying to measure oral health in such an age group. The local Family Health Services Authority lists, based on registrations with general medical practices, were used as sampling frames. These proved to be straightforward to manipulate and are believed to be almost complete for the population at this age. Final samples of around 800 individuals in each area were visited at home, representing 53-62 per cent of all subjects who could be contacted, except in one subgroup where only 39 per cent of contacts permitted a visit. There were problems related to difficulty making contact with a proportion of the names sampled. This may have resulted from list errors, illnesses and unrecorded changes of address. A letter from the subjects' family doctors appeared to be an important factor influencing response rates. Systematic bias among subjects refusing a visit was assessed using a follow up postal questionnaire which showed that the edentulous were under-represented in the final (visited) sample by 1-10 per cent, whilst the dentate non-attenders were under represented by 2-13 per cent.
Aged↗
The effect of glass ionomer cement on the surface hardness of resin based materials.
The potential interaction between resin-based materials and glass ionomer cements was investigated by comparing the hardness of the non-adjacent surface of two different resin materials when cured over the cements. Control specimens were made by curing the resin materials over an acrylic surface. Two glass ionomer cements were tested and neither were shown to cause a significant reduction in the surface hardness of either of the resin based materials. The 0.5 mm thick specimens of both resin based materials were significantly softer than the thicker specimens irrespective of the base material.
Analysis of Variance↗
The influence on partial denture design of a teaching video for general dental practitioners.
This evaluation was based on replies from a random sample of general dental practitioners who were asked to complete questionnaires before and after being sent a video and accompanying booklet on partial denture design. Forty per cent (257) of the original sample (636) completed and returned both questionnaires. A total of 212 respondents (82%) felt the video had been of value and 175 (68%) said they would be more likely to provide metal partial dentures after having watched it. The positive effects of the video were greatest amongst the most recently qualified. Despite some improvement after watching the video, there remained 105 (40%) who indicated that they would leave all partial denture design decisions to the technician on at least some occasions. Comparison of data from first and second questionnaires showed little evidence of substantial shifts in choice of denture design for a series of specific situations. It was concluded that whilst the programme had been well received and had produced changes in intention, there was less objective evidence of change.
Acrylic Resins↗
Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas.
BACKGROUND: Aberrations of the p53 gene (also known as TP53) frequently lead to the synthesis of mutant proteins that accumulate in the nuclei and/or cytoplasm of neoplastic cells. Intracellular p53 protein accumulation may be an unfavorable prognostic parameter in breast, lung, ovarian, gastric, and colorectal cancers. Specific classes of p53 gene mutations, assayed by characteristic subcellular p53 protein accumulation patterns, may be useful prognostic indicators. PURPOSE: The prognostic value of nuclear and cytoplasmic p53 protein accumulation in the tumor cells of patients with colorectal carcinoma was studied. METHODS: Antibodies PAb 1801 and CM1 were used for immunocytochemical assay of nuclear and cytoplasmic p53 protein accumulation in a retrospective series of colorectal carcinoma samples obtained from 206 patients who were followed for at least 5 years. Results were correlated with the following clinicopathologic parameters: patient sex and age; tumor site, stage, and grade; and DNA ploidy status of the tumors. Overall survival and disease-free survival were analyzed with the Kaplan-Meier method. Differences in distributions were analyzed using the Mantel-Cox method. Multivariate analysis was performed with the Cox proportional hazards model. RESULTS: Immunostaining with PAb 1801 revealed nuclear p53 accumulation in 46% (95) of 206 cases, whereas CM1 immunostaining of 197 cases showed nuclear and cytoplasmic p53 accumulation in 33% (65 cases) and 50% (99 cases) of the cases, respectively. In univariate analysis, both nuclear p53PAb 1801 and cytoplasmic p53CM1 protein accumulations were significantly associated with poor overall survival (P = .0198 and P = .0017, respectively) and with disease-free survival (P = .004 and P = .0016, respectively). When patients were analyzed according to site of their tumors, nuclear p53PAb 1801 protein accumulation was statistically significant only in the right colon (P = .027), whereas cytoplasmic p53CM1 protein accumulation was statistically significant in the left colon and rectum (P = .0016). In multivariate analysis, only cytoplasmic p53CM1 protein accumulation was associated with poor overall survival and with disease-free survival (P = .006 and P = .002, respectively). With the addition of DNA ploidy status, however, cytoplasmic p53CM1 protein accumulation remained significant only for disease-free survival (P = .035). In patients with tumors of the left colon and rectum, cytoplasmic p53CM1 protein accumulation was the most significant prognostic indicator for overall survival (P = .007) and disease-free survival (P = .002) after disease stage. CONCLUSION: Cytoplasmic p53CM1 protein accumulation, but not nuclear p53PAb 1801 protein accumulation, is an independent prognostic parameter in patients with colorectal carcinomas. IMPLICATIONS: Cytoplasmic p53CM1 accumulation may be a useful indicator of patients at high risk for disease recurrence who may benefit from aggressive adjuvant therapy.
Adenocarcinoma↗
Long-term human vein graft contractility and morphology: a functional and histopathological study of retrieved coronary vein grafts.
Vasoreactivity of 11 coronary artery vein bypass grafts and 13 human saphenous veins was examined. Isometric tension studies were performed in response to potassium chloride (110 mmol/l), noradrenaline (10(-9)-10(-4) mol/l), serotonin (10(-9)-10(-4) mol/l) and histamine (10(-8)-10(-2) mol/l). After precontraction with noradrenaline (10(-5) mol/l), the response to acetylcholine (10(-8)-10(-4) mol/l) and the calcium ionophore A23187 (10(-8)-10(-4) mol/l) was also assessed. Results are given as mean(s.e.m.). Compared with saphenous veins, vein grafts showed decreased sensitivity to noradrenaline (1.7(0.5) versus 0.4(0.1) mumol/l, P = 0.01), no change in sensitivity to serotonin (55(18) versus 37(15) mumol/l, P > 0.05) and supersensitivity to histamine (3.2(0.9) versus 30.1(13.2) mumol/l, P = 0.01). Vein grafts had a decreased maximal contraction to potassium chloride (1.1(0.3) versus 5.5(0.8) g, P = 0.0001), noradrenaline (1.2(0.3) versus 4.1(0.8) g, P = 0.005), histamine (1.2(0.3) versus 4.5(0.8) g, P = 0.003) and serotonin (0.7(0.2) versus 5.7(0.6) g, P = 0.0002) compared with saphenous vein. Precontracted vein grafts did not relax in response to acetylcholine; in contrast, saphenous vein relaxed in a dose-dependent manner to a maximal relaxation of 22(3) per cent. Both saphenous vein and vein graft relaxed in response to A23187. Vein graft intimal thickness was approximately fourfold greater than that of saphenous vein (540(110) versus 136(30) microns). Scanning electron microscopy of vein and vein graft revealed an intact endothelium. Coronary artery vein grafts are capable of responding to various contractile agonists; these response are notably different from those of saphenous vein and there is a loss of endothelium-dependent relaxation. Even at a late stage vein grafts are not inert but are functional conduits with an abnormally responsive endothelium and a less potent, but significantly altered, smooth muscle contractile profile.
Aged↗
Fertility and sexual and gynecologic function after ileal pouch-anal anastomosis.
PURPOSE: This study was designed to determine the incidence of infertility, gynecologic problems, and sexual dysfunction after ileal pouch-anal anastomosis (IPAA). METHODS: A questionnaire was sent to 206 females who underwent pouch surgery at a single institution from 1980 through 1991. Response rate was 53 percent (110/206). The computerized registry of the 206 females undergoing IPAA at this institution was reviewed to add additional data. RESULTS: Mean age at pouch construction was 32 (range, 14-61) years. Mean time from pouch surgery to survey was 49 (range, 1-132) months. Fifty-seven females had 119 children before pouch surgery, and 23 children were born to 19 females after IPAA (5 vaginal deliveries, 18 Cesarean sections). Eighteen females experienced infertility after IPAA. Thirty patients had persistent dyspareunia. Pelvic cysts developed in 15 patients; 11 patients required surgery. CONCLUSIONS: Although childbirth appears safe, gynecologic problems, such as dyspareunia and formation of pelvic cysts, may be underestimated after IPAA. The effects of IPAA on fertility are still unknown.
Adolescent↗