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Biomedical subjects

M M Henry

Publications and source records attributed to M M Henry.

At least 37 records · Page 2Linked to original sources

Nasal lavage cytokines in normal, allergic, and asthmatic school-age children.

Inflammation can be demonstrated in the airway mucosa of asthmatics, even in the absence of overt symptoms, but the pathogenesis of this chronic inflammation is incompletely defined. It has been suggested that inflammatory cytokines produced by epithelium may play important roles in this process. Therefore, we measured the cytokines interleukin-8 (IL-8), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in nasal lavage fluids from school-age children who were (1) "normal" (nonallergic/nonasthmatic), (2) allergic to house-dust mite antigen but nonasthmatic (no history of wheezing), or (3) allergic and asthmatic (history of > or = 10 wheezing episodes). Children underwent a single nasal lavage procedure while asymptomatic and on no anti-inflammatory medications or anti-histamines. In addition to cytokine concentrations, cell counts, differentials, albumin, histamine, and eosinophil cationic protein (ECP) concentrations were determined in nasal lavage fluids. Significant increases in IL-8 and ECP were observed in asthmatics compared with both normals and allergic nonasthmatics. Overall, IL-8 in nasal lavage fluids correlated significantly with ECP. Allergic nonasthmatics did not have significant increases in cytokines or other mediators compared with normal subjects. Concentrations of IL-6 did not differ significantly among the three groups, and GM-CSF was undetectable in all samples tested. We conclude that increased IL-8 production and eosinophil activation are characteristic of the airways of asthmatic children when asymptomatic, and we speculate that IL-8 plays a role in the maintenance of airway inflammation in asthma.

Adolescent↗

The range of PaO2 variation determines the severity of oxygen-induced retinopathy in newborn rats.

PURPOSE: This study was conducted to determine the potential influence of PaO2 fluctuation on the retinal neovascular response known to occur in newborn rats exposed to hyperoxic conditions. As an inherent corollary, the authors also defined the relationship between the fraction of inspired oxygen (FiO2) and the arterial blood oxygen tension (PaO2) in newborn rats. METHODS: Experiment 1 was composed of several oxygen-exposure protocols in which atmospheres of 10% oxygen concentration were alternated with different higher levels of ambient oxygen (50%, 40%, 30%, and room air). In experiment 2, two alternating oxygen concentrations were made to converge toward room air (20.9% oxygen) with each successive group of four treatment groups. These included another group exposed to alternating 50% and 10% oxygen, a group exposed to alternating 45% and 12.5% oxygen concentrations, one exposed to alternating concentrations of 40% and 15% oxygen, and a final group exposed to 35% and room air oxygen concentrations. In each case, oxygen was alternated between the two exposure concentrations every 24 hours. The term delta FiO2 is used to designate the difference in the two oxygen concentrations to which a treatment group was subjected, applying the units of fraction of inspired oxygen (i.e., delta FiO2 = 0.4 for the exposure to alternating 50% and 10% oxygen). At birth, litters of albino rats were placed in each of these environments for 13 or 14 days, after which PaO2 and retinal vascular development were assessed in some rats. The remainder were removed to room air for 4 days before the incidence and severity of abnormal neovascularization were measured. RESULTS: PaO2 and FiO2 were directly and linearly correlated (r2 = 0.998). In experiment 1, the extent of retinal vascular development on removal from oxygen was a linear function of delta FiO2. Retinal neovascularization subsequently occurred in all rats exposed to alternating 50% and 10% or 40% and 10% oxygen concentrations, but only a third of the 30% and 10% exposure group, indicating a minimum threshold for proliferative disease at delta FiO2 = 0.2. In experiment 2, retinal avascularity also increased linearly with increasing delta FiO2. There was a threshold for neovascularization between the exposure to alternating 45% and 12.5% oxygen and the 40% and 15% oxygen exposure (100% versus 4.8% incidence of neovascularization), indicating a requirement of < or = 12.5% oxygen episodes to stimulate a consistent proliferative response. CONCLUSIONS: These results suggest that PaO2 fluctuation and degree of hypoxia may have more influence on proliferative retinal disease in newborn rats than the extended hyperoxia that has historically received greater attention. Experimental designs that address the inherent differences in pulmonary function between intrinsically healthy animals and compromised premature infants are of substantial value to our understanding of the pathogenesis of retinopathy of prematurity.

Animals↗

Effect of age, sex and parity on anorectal function.

Ninety-one healthy subjects (51 women; age range 16-85 years) were studied prospectively to determine the effect of age, sex and parity on anorectal function. Maximum resting pressure, voluntary contraction pressure, rectal sensation to distension, rectal and mid-anal electrosensitivity, perineal descent, pudendal nerve terminal motor latency and fibre density of the external and sphincter were measured. Sex influenced mean(s.d.) voluntary contraction pressure (148(56) versus 95(43) cmH2O for men versus women, P < 0.0001), perineal descent on straining (1.0(0.5) versus 1.3(0.4) cm, P = 0.02) and fibre density (1.43(0.14) versus 1.52(0.15), P = 0.02). Age influenced resting pressure (r = -0.43, P = 0.0001), perineal position at rest (r = -0.55, P < or = 0.0001), mid-anal electrosensitivity (r = 0.42, P = 0.0001) and rectal electrosensitivity (r = 0.54, P < 0.0001). Parity affected mean(s.d.) voluntary contraction pressure (105(53) versus 75(20) cmH2O for nulliparous versus parous women, P = 0.04) and mid-anal electrosensitivity (5.3(2.3) versus 4.5(2.3) mA, P = 0.02). Increasing age leads to perineal descent at rest, slowed pudendal nerve conduction, a fall in resting anal pressure and decreased anorectal sensory function. Women have a lower and squeeze pressure, greater perineal descent, longer pudendal nerve terminal motor latency and a greater muscle fibre density than men. Parity leads only to lower squeeze pressure.

Adolescent↗

Audit of postanal repair in the treatment of fecal incontinence.

PURPOSE: The short-term results of postanal repair for idiopathic fecal incontinence are satisfactory but data on long-term outcome are lacking. This study was carried out to document the short-term and long-term results of this operation and to determine whether preoperative tests predict long-term outcome. METHODS: Thirty-six patients (33 females; mean age, 57 years) with major idiopathic fecal incontinence operated on by one surgeon were studied. Patients had resting and voluntary contraction anal pressures and pudendal nerve terminal motor latencies (PNTML) measured preoperatively. Symptoms were evaluated at 6 months after operation and again at a median of 25 (range, 6-72) months in all 36 patients. Symptoms were classified as: Group C, no improvement or worse; Group B, minor improvement; and Group A, marked improvement in comparison to the patient's preoperative symptoms. Seventeen patients had postoperative physiology performed. RESULTS: At 6 months there were 6 (17 percent) patients in Group C, 12 (33 percent) in Group B, and 18 (50 percent) in Group A. At final follow-up there were 17 (47 percent) in Group C, 9 (25 percent) in Group B, and 10 (28 percent) in Group A. Comparison of the preoperative data in the final outcome groups showed (mean +/- SE): Groups A and B vs. Group C--resting pressure, 24.6 +/- 6 cm H2O vs. 40.5 +/- 12.2 (P = 0.2), voluntary contraction pressure, 23.7 +/- 5.7 vs. 11.8 +/- 3.6 (P = 0.09), and PNTML, 3.2 +/- 0.75 mS vs. 3.3 +/- 0.99 (P = 0.8). Mean differences between post-operative and preoperative results were: resting pressure, 28 +/- 8.2 cm H2O (P = 0.003); voluntary contraction pressure, 19.5 +/- 6.7 (P = 0.01); and PNTML, -0.3 +/- 0.29 mS (P = 0.3). CONCLUSIONS: At 6 months 83 percent of patients had obtained some benefit from postanal repair but only 53 percent maintained this improvement with only 28 percent being markedly better. There was a trend toward a more favorable outcome in patients with greater squeezing pressures preoperatively but other tests were not of long-term predictive value.

Anal Canal↗

Bowel dysfunction: a pathogenic factor in uterovaginal prolapse and urinary stress incontinence.

OBJECTIVE: To investigate the aetiological importance of bowel dysfunction in patients with uterovaginal prolapse and urinary stress incontinence. DESIGN: Observational study using a questionnaire about obstetric history and bowel function, and anorectal physiological studies. SETTING: Physiology unit and gynaecological outpatients departments of two teaching hospitals. SUBJECTS: Twenty-three women with uterovaginal prolapse (mean age 57 years), 23 women with urinary stress incontinence (mean age 52 years) and 27 control women (mean age 52 years). RESULTS: There was no statistically significant difference between the three groups in their parity, age or birthweight of their children. However, straining at stool as a young adult prior to the development of urogynaecological symptoms was significantly more common in women with uterovaginal prolapse (61% vs 4%, P < 0.001) and women with urinary stress incontinence (30% vs 4%, P < 0.05), compared with controls. A bowel frequency of less than twice per week as a young adult was also more common in women with uterovaginal prolapse than in control women (48% vs 8%, P < 0.001). At the time of consultation, 95% of the women with uterovaginal prolapse were constipated, compared with only 11% of control women. Many of these women also needed to digitate to achieve rectal evacuation. Compared with controls, women with uterovaginal prolapse had a prolonged pudendal nerve terminal motor latency (1.9 ms vs 2.2 ms, respectively, P = 0.003). Women with stress incontinence of urine had a normal pudendal nerve latency (2.0 ms). Other tests of anorectal function were normal. CONCLUSIONS: Constipation, in addition to obstetric history, appears to be an important factor in the pathogenesis of uterovaginal prolapse.

Adult↗

Pelvic floor function in multiple sclerosis.

The aim of this study was to define pelvic floor function in patients with multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation difficulties without incontinence (MSC). Normal controls and patients with idiopathic neurogenic faecal incontinence without multiple sclerosis (FI, disease controls) were also studied. Thirty eight multiple sclerosis patients (20 incontinent, 18 incontinent) 73 normal controls, and 91 FI patients were studied. The FI group showed the characteristic combined sensorimotor deficit previously described in these patients of low resting and voluntary contraction and pressures, increased sensory threshold to mucosal stimulation, and increased pudendal nerve terminal motor latencies and fibre densities. MSI patients had significantly lower anal resting pressures (80 (30-140) cm H2O, median (range) v 98 (30-200), normal controls, p = 0.002) and both MSC and MSI patients had significantly lower anal maximum voluntary contraction pressures (65 (0-260) cm H2O, MSC and 25 (0-100), MSI v 120 (30-300), normal controls, p = < 0.0004) and higher external anal sphincter fibre densities (1.7 (1.1-2.6), MSC and 1.7 (1.1-2.4), MSI v 1.5 (1.1-1.75), normal controls, p < 0.006) compared with normal controls but pudendal nerve terminal motor latencies were similar and no sensory deficit was found. This contrasted with the idiopathic faecal incontinent patients who, in addition to significantly higher fibre densities (1.8 (1.1-3), p = 0.001) had increased pudendal latencies (2.5 (1.1-5.5) mS v 2.08 (1.4-2.6), p = 0.001) compared with normal controls. The idiopathic faecal incontinent group had significantly lower resting anal pressures (50 (10-160) cm H2O, p=0.02) than the MSI group. Comparison with the incontinent and continent multiple sclerosis groups showed that incontinence was associated with lower voluntary anal contraction pressures (25 (0-100) v 65 (0-260), p=0.03) but that there were no other differences between these two groups. Pelvic floor function is considerably disturbed in multiple sclerosis, showing muscular weakness with preservation of peripheral motor nerve conduction, providing indirect evidence that this is mainly a result of lesions within the central nervous system.

Adult↗

Defecography in multiple sclerosis patients with severe constipation.

PURPOSE: To evaluate defecography in assessment of anorectal function in patients with multiple sclerosis (MS) who have intractable constipation. MATERIALS AND METHODS: Eleven patients with MS and constipation (10 women, one man) underwent defecography. A total of 130 mL of barium, liquid (20 mL) and paste, was introduced into the rectum. A dab of barium marked the external anal orifice, and, in the women, a tampon soaked with contrast medium marked the vagina. Video radiographic images and supplemental 100-mm static camera images were obtained. RESULTS: During defecation, six patients had no puborectalis muscle effacement, four patients had partial effacement, and one patient had complete effacement. No rectal emptying occurred in five patients, and emptying was incomplete in the rest. Three patients developed an intussusception, and two developed a posterolateral pouch. CONCLUSION: Defecography readily demonstrates rectal outlet obstruction and the failure of the puborectalis and anal sphincter muscles to relax. These are frequent findings in MS patients with intractable constipation.

Anal Canal↗

Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat.

Exposure to variable hyperoxia has recently been shown to be much more effective at producing proliferative retinopathy in the newborn rat than exposure to constant hyperoxia. To incorporate a more clinically relevant oxygen-exposure paradigm in our studies, we have now used a cycle between 50 and 10% oxygen and have compared its effects with those found using new exposures to the previously used 80/40% cycle. Starting at birth and continuing for 14 d, rats were exposed to environments that cycled between 50 and 10% oxygen or 80 and 40% oxygen every 24 h. After exposure, some rats were killed for assessment of retinal vascular development. Others were removed to room air for 4 d before killing and evaluation for the presence of abnormal neovascularization--a clinical consequence believed to be promoted by termination of oxygen therapy. The 50/10% cycle resulted in greater retardation of retinal blood vessel development during oxygen than that found in the 80/40% exposure group. After 4 d postexposure in room air, the incidence of preretinal neovascularization was 97% in the 50/10% rats and 72% in the 80/40% group. Clearly, the overall amount of oxygen the subject receives is less critical than other parameters of its administration in producing proliferative retinopathy. Also, the range of variation (40% in both cases) is not the controlling characteristic. Our results suggest that consistency of oxygen level and avoidance of hypoxic levels should be important concerns in neonatal oxygen therapy.

Animals↗

The role of pudendal nerve innervation in female pelvic floor function.

The assessment of motor conduction along the pudendal nerve is an accurate objective measure of pudendal nerve function. Measurement of its latency (that is the time interval between electrical stimulation of the nerve and induced contraction of the external anal sphincter) has been demonstrated to be abnormally long following vaginal delivery, particularly if the delivery was associated with a heavy fetus or a prolonged second stage of labor. The significance of pudendal neuropathy and its relationship to abnormal degrees of descent of the pelvic floor have also been examined in this review.

Fecal Incontinence↗

Oxygen-induced retinopathy in the rat: relationship of retinal nonperfusion to subsequent neovascularization.

PURPOSE: To confirm a relationship between oxygen-induced retinal vasoattenuation and subsequent abnormal neovascularization in the newborn rat. METHODS: Beginning at birth, some litters of Sprague-Dawley rats were exposed to 80% constant oxygen while others received oxygen varying between 40% and 80% in a cyclic fashion. The frequency of the change in inspired oxygen (FiO2) was either 6, 12, 24, or 48 hours. The exposures periods lasted for 14 days, at which time some rats from each exposure group were sacrificed and assessed for retinal vasoattenuation with injection of fluorescein-labeled dextran. The remaining rats from each group were transferred at day 14 from the hyperoxic atmosphere to room air for an additional 4 days. These animals were then killed and assessed for retinal neovascularization by staining for vascular ADPase activity. RESULTS: Of all rats raised in variable oxygen, 62% exhibited abnormal retinal neovascularization after 4 days in room air. Only 18% of the rats exposed to constant oxygen responded with abnormal neovascularization. Among the four groups of variable oxygen-exposed rats, there was a direct correlation (R2 = 0.96) between degree of retinal avascularity upon removal from oxygen and the propensity for subsequent abnormal neovascularization. Constant oxygen-exposed rats did not exhibit this relationship. This exposure produced the greatest retinal avascularity upon removal from oxygen but the lowest incidence of abnormal neovascularization after 4 days in room air. CONCLUSIONS: Retinal avascularity may not be the single overriding stimulus for neovascularization in oxygen-induced retinopathy. Other hypotheses bear consideration, including the possibility that variable oxygen leads directly to vascular endothelial cell mitosis, a common retinal manifestation of ischemia-reperfusion.

Animals↗

Neuropeptides in the internal anal sphincter in neurogenic faecal incontinence.

The internal anal sphincter has both an intrinsic and extrinsic innervation which modulates its activity. While the nature of the extrinsic innervation has been well characterised, the same is not true of the intrinsic innervation. Although a variety of neurotransmitters have been identified in the human internal anal sphincter, their physiological role in health, and possible involvement in disease processes, have received little attention. Using immunohistochemistry we have studied the distribution and nerve fibre densities of a range of neuropeptides in the internal anal sphincter from 12 cancer patients (controls) and from 16 patients with neurogenic faecal incontinence. We have also studied the in vitro effect of vasoactive intestinal peptide, neuropeptide tyrosine, and galanin on isolated preparations of the internal anal sphincter from 11 cancer controls and 5 patients with neurogenic faecal incontinence. There was no difference in either the distribution or density of the neuropeptides between the 2 groups of patients, and there was no qualitative difference in the in vitro responses of the sphincter to the neuropeptides. These findings suggest that these neuropeptide components of the intrinsic innervation of the internal anal sphincter are unaffected in patients with neurogenic faecal incontinence.

Anal Canal↗

Abnormalities of innervation of internal anal sphincter in fecal incontinence.

Physiological and histological studies have shown that the internal and sphincter is abnormal in idiopathic fecal incontinence. We have recently demonstrated that the in vitro contractile response of the internal anal sphincter to the sympathetic neurotransmitter noradrenaline is decreased in incontinence. In this study we have further defined this reduced sensitivity and provided more information about the intrinsic innervation in both the normal and the incontinent sphincter muscle. Muscle strips from 12 incontinent patients undergoing post and repair and from 11 controls undergoing rectal excision for low rectal carcinoma were studied. Responses to noradrenaline were recorded initially alone and then in the presence of phentolamine, an alpha-adrenoceptor blocker. In the presence of phentolamine, noradrenaline caused relaxation: there was no significant difference in the relaxation-response curves and the EC50 was the same in the two groups. These results demonstrate that the previously documented reduced sensitivity to noradrenaline is due to an altered sensitivity of the alpha-adrenoceptors. Electrical field stimulation produced relaxations in all muscle strips, but only in the controls was the magnitude of the relaxation significantly increased in the presence of phentolamine. This indicates that there is an alpha-adrenergic excitatory component of the response to electrical field stimulation of the intramural nerves, which was present in tissues from control patients but which was absent in tissues from patients with idiopathic fecal incontinence.

Anal Canal↗

Laparoscopic assisted surgery of the colon. Operative technique.

Laparoscopic cholecystectomy is the most common major abdominal operation performed endoscopically. Other surgical procedures performed endoscopically include hysterectomy, hernia repair, Nissen fundoplication, and vagotomy. More recently, laparoscopic colectomy has been described (1,2). We have performed over fifty laparoscopic assisted colonic procedures, the results of which have been published (2). In this paper we describe the technique of two laparoscopic assisted procedures in colonic surgery--right and left hemicolectomy.

Anastomosis, Surgical↗

Antemortem diagnosis of cholangiocellular carcinoma in a horse.

A 10-year-old Tennessee Walking Horse gelding was admitted to the veterinary teaching hospital for evaluation of intermittent fever, lethargy, and anorexia. Initial laboratory analyses revealed anemia and hyperfibrinogenemia. Abdominocentesis and thoracentesis yielded fluid samples with high nucleated cell counts and total protein concentrations. The tentative diagnosis was nonseptic peritonitis. The horse did not improve after 4 days of antimicrobial treatment, and pitting edema of the ventral midline developed. Thoracic radiography and ultrasonography revealed consolidation of the ventral aspect of the lung fields and pleural effusion. Pleuroscopy of the right hemithorax revealed pleural effusion and a soft-tissue mass in the caudal portion of the mediastinum. Findings on biopsy of the liver and mediastinal mass led to a presumptive diagnosis of metastatic cholangiocellular carcinoma. The horse was euthanatized, and the diagnosis was confirmed at necropsy.

Animals↗

Decreased sensitivity of muscarinic but not 5-hydroxytryptamine receptors of the internal anal sphincter in neurogenic faecal incontinence.

Previous studies of the internal anal sphincter in patients with neurogenic faecal incontinence have indicated an abnormality of the adrenergic innervation, but little is known about the responsiveness of other receptors in the internal and sphincter in this condition. In this study the in vitro sensitivity to carbachol and 5-hydroxytryptamine (5-HT) of muscle strips from patients with neurogenic incontinence (n = 6 and n = 7) and from control patients (n = 9 and n = 10) was examined. Preparations of internal and sphincter from patients with incontinence were less sensitive to the relaxant actions of carbachol than preparations from the control group. The pD2 value for carbachol (i.e. the negative logarithm of the concentration for half-maximal response) was significantly greater in the controls than in the incontinent group (mean(s.e.m.) 6.03(0.15) versus 5.43(0.24), P < 0.05). There was no significant difference in the contractile responses to 5-HT, which had pD2 values of 6.93(0.13) and 6.63(0.27) for the control and incontinent groups respectively. The unaffected state of the 5-HT receptor and the subsensitivity of the muscarinic receptor are discussed in relation to intrinsic neural control of the internal and sphincter in neurogenic faecal incontinence.

Adult↗

Oral or intravenous erythromycin has no effect on human distal colonic motility.

Erythromycin is a prokinetic agent for the lower oesophageal sphincter, the stomach, the gallbladder and the small bowel, acting directly on motilin receptors. Its effect on pressure activity of the human colon has not been investigated. Eight healthy volunteers were studied on 2 occasions and given intravenous or oral erythromycin, or placebo in a single-blind, randomized crossover study. Sigmoid pressure activity was measured using a 4-lumen water perfused system placed sigmoidoscopically at 50, 45, 30 and 15 cm from the anal verge. The pressures were analysed for activity index (mmHg.min) for the 35 cm colonic study segment using dedicated software. No significant difference was found in the activity index following oral erythromycin (500 mg) or placebo, or following intravenous erythromycin 1.8 mg/kg or placebo. A further 8 subjects were studied in a single-blind crossover study to determine the effect of oral erythromycin (500 mg) b.d. on colonic transit, measured with radio-opaque markers and a single abdominal X-ray. Mean or segmental colonic transit times were not statistically significantly different (Student's paired t-test) in the subjects on placebo or erythromycin. This lack of effect of erythromycin on the distal large intestine may indicate the absence of receptors for motilin in that part of the gut.

Administration, Oral↗