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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 271 records · Page 15Linked to original sources
PubMed1993

Influence of prior radiotherapy on the development of postoperative complications and success of free tissue transfers in head and neck cancer reconstruction.

The purpose of this study was to determine whether prior radiotherapy had any effect on the development of postoperative complications in patients undergoing microvascular tissue transfers for reconstruction of head and neck cancer. A prospective database was used to review 354 consecutive patients who had a total of 368 free tissue transfers limited to the head and neck during the 4-year period from July 1988 to June 1992. Postoperative complications in 167 patients who received preoperative radiotherapy (XRT) were compared with those of 187 patients who did not undergo radiotherapy preoperatively (NR). No statistical differences in complications or flap loss between the two groups were noted using the chi 2 test or Fisher's exact test (p > 0.2). Total flap loss occurred in 5.3% of the XRT group (9 of 169) and 5.0% of the NR patient group (10 of 199), and partial flap loss occurred in 4.1% of the irradiated patients and 2.5% of the nonirradiated patients. Major wound complications requiring additional surgery occurred in 16% of the XRT group and 11% of the NR group. Minor wound complications that did not require further surgery occurred in 21% of the irradiated patients and 18% of the nonirradiated patients. No significant difference in the timing or dose of preoperative radiation, previous neck dissection, or anastomotic type could be documented in failed versus successful flaps (two-tailed t-test, p > 0.80, and chi 2, p > 0.2). Our results show that, in a large group of cancer patients undergoing free tissue transfers to the head and neck, prior radiotherapy or surgery did not predispose them to a higher rate of acute flap loss or wound complications than their nonirradiated cohorts.

Adolescent↗
PubMed1993

Osseous free flaps for orbit and midface reconstruction.

Osseous free flaps were used for reconstruction of the orbit and midface in 10 patients. The reconstruction was done at the time of tumor resection in two patients (20%) and secondarily in eight patients (80%). Nine patients (90%) had previously received radiotherapy. The flaps used were fibula (four), radial forearm (two), scapula (two), and split iliac crest (two). Flap loss occurred in one patient. Complications occurred in 2 of 10 (20%) patients. The results were classified as good in seven patients, fair in two, and poor in one. The patient classified as having a poor result was the one who sustained the flap loss; he refused further surgery. Reconstruction was directed to the maxilla in five patients, the orbit in two, and both in three. The radial forearm flap was best used for orbit-only reconstruction because of the small amount of bone required. The fibula, iliac crest, and scapula were best used for larger defects involving the maxilla. Osseointegrated dental implants were used successfully in three patients. Osseous free flaps are indicated for midface reconstruction when bony support is needed and previous irradiation prevents the use of nonvascularized grafts.

Adolescent↗
PubMed1993

Increased respiratory drive as an inhibitor of oral feeding of preterm infants.

This study was designed to determine whether increased respiratory drive induced by inhalation of carbon dioxide would alter the reflex and voluntary components of feeding. For 10 preterm infants (mean +/- SD: postconceptional age at study, 34 +/- 2 weeks; weight, 2.1 +/- 0.2 kg), four trials of nutritive feeding were offered: two while the infants were inhaling a gas mixture containing 40% oxygen and two while the infants were breathing 40% oxygen and 7% carbon dioxide. Nasal airflow was monitored with a pneumotachygraph. Pressure-sensitive catheters in the esophagus and in the feeding nipple were used to detect swallowing and sucking. Sucking frequency and pattern, rate of swallowing, end-tidal carbon dioxide, and minute ventilation were recorded for 30-second epochs during feeding. When the inhaled gas mixture was switched from 40% oxygen to 40% oxygen and 7% carbon dioxide, sucking frequency decreased from 53 +/- 10 to 48 +/- 12 and from 54 +/- 12 to 40 +/- 19 sucks/min, respectively (p < 0.005). Frequency of swallowing also fell during the two feeding epochs on 7% carbon dioxide, from 45 +/- 15 to 40 +/- 15 and from 43 +/- 14 to 31 +/- 16 swallows/min (p < 0.003). Thus acute hypercapnea was accompanied by a decrease in rate of both sucking and swallowing during nutritive feeding. Increased ventilatory drive may directly inhibit nutritive feeding behavior in premature infants.

Bottle Feeding↗
PubMed1993

Interposition vein grafting in head and neck reconstructive microsurgery.

To characterize the role of interposition vein grafts, and to determine whether their use significantly influences the success of free tissue transfers in head and neck cancer reconstruction, we reviewed 191 consecutive cases with defects involving the aero-digestive tract soft tissues (80), the mandible (75), craniofacial resections (25), or cutaneous coverage (11). One hundred twenty patients had received prior loco-regional therapy, including 63 patients with recurrent lesions. Interposition vein grafts were used for the artery (11), vein (3), or both (3) in a total of 17 cases. The overall technical success rate was 93.2 percent (178/191). Cases in which vein grafts were used had a significantly (p < 0.001) lower success rate, 70.6 percent (12/17), than those without vein grafts, 95 percent (166/175). Grafts were most often used in patients who had received prior therapy (13/17). The use of vein grafts was associated with a significantly higher incidence of flap failure in head and neck cancer reconstruction; however, a causal relationship is not suggested.

Adult↗
PubMed1993

Human non-secretory ribonucleases. I. Purification, peptide mapping and lectin blotting analysis of the kidney, liver and spleen enzymes.

Human non-secretory neutral ribonucleases (RNases) from kidney, liver and spleen have been purified and characterized. SDS-PAGE indicates that all three RNases are highly purified and have apparent mol. wts of 17-18 kDa. Kinetic analysis indicates that all three RNases have a broad pH optimum centred around 6.5, and all three have similar substrate specificities with significant preference for RNA and poly(U) when compared to poly(C), poly(A) and poly(G). All of the above data, as well as immunoblotting data using three polyclonal antibodies (anti-human liver RNase, anti-human pancreatic RNase, anti-human eosinophil-derived neurotoxin), indicate that the three proteins are highly purified and are non-secretory RNases (IIN). Further characterization by cyanogen bromide peptide mapping and extensive lectin blotting indicated no significant differences between the three human RNases. All three RNases appear to have very similar, if not identical, protein backbones and all three are glycoproteins which are recognized by lectins with specificity for GlcNAc, Fuc and, to a lesser extent, with specificity for Gal beta(1-4)GlcNAc. No significant tissue-specific differences were found among the three human non-secretory RNases.

Blotting, Western↗
PubMed1993

An evaluation of the efficacy of postoperative irradiation in rectal adenocarcinoma.

Cancer of the colon and rectum is the second most common form of cancer in the United States. Although surgery is the primary treatment for rectal cancer, the overall 5-year survival approximates 50%. Pelvic failure rates and their associated morbidity have led to the use of postoperative irradiation, either alone or combined with chemotherapy. We reviewed 77 consecutive patients treated with postoperative irradiation to the pelvis following curative surgery. The prognosis is dependent on surgical stage and histologic grade. The minimal decrease in local recurrence in this study is offset by treatment-related small bowel injury. A subset of patients who may benefit from adjuvant treatment is yet to be defined.

Adenocarcinoma↗
PubMed1993

Urinary nitrite excretion in premature infants: effects of transfusion or indomethacin.

Urinary nitrite excretion, an index of L-arginine-dependent nitric oxide formation, was quantified daily for two weeks, in very low-birth-weight (< 1500 g) premature infants. A transient 52% reduction in nitrite excretion was noted on the day of transfusions (54 +/- 10 versus 26 +/- 6 mumol/mmol creatinine, before and during transfusion, respectively, n = 24, p < 0.02). Indomethacin administration in six infants was associated with a dramatic increase in nitrite excretion from a basal median value of 3 to 76 mumol/mmol creatinine (p < 0.05). Nitrite excretion returned to baseline on day 3 after indomethacin administration. In two infants who received indomethacin and transfusions on the same day, the stimulatory effect on nitrite excretion by indomethacin overwhelmed any depressive effect of transfusions. These results suggest that L-arginine utilization is influenced by common therapeutic strategies in these high-risk infants.

Blood Component Transfusion↗
PubMed1993

Substance P levels in experimental ileitis in guinea pigs: effects of misoprostol.

Substance P, a neuropeptide mediator of inflammation, was quantified during the evolution of trinitrobenzene sulfonic acid (TNBS)-induced ileitis in guinea pigs. Ileitis was induced by a single intraluminal injection of TNBS (30 mg/kg in 50% ethanol). Misoprostol, a prostaglandin E1 analogue, was administered parenterally (30 mg/kg sc twice daily) in a group of TNBS-treated animals. Control guinea pigs received intraluminal saline (sham) or 50% ethanol (TNBS vehicle). Guinea pigs were evaluated at day 1, 3, 7, 14, or 30 after ileitis induction for substance P content (radioimmunoassay) and distribution (immunohistochemistry), morphology, myeloperoxidase (MPO) activity, and protein leak into the gut lumen. TNBS administration caused an increase in ileal MPO activity that peaked at day 7 and increased mucosal leak of protein. Misoprostol attenuated the granulocyte infiltration (MPO) response to TNBS but exacerbated the mucosal leak of protein. Substance P levels in whole ileal segments were unaltered from baseline on day 1 in all groups. On day 3 a marked decrease in ileal substance P content was evident in the TNBS and TNBS + misoprostol groups. As early as day 1, immunohistochemistry suggested that the decreased substance P content was confined to the mucosa and submucosa, because myenteric plexus staining was not reduced. Loss of staining in the perivascular nerves was particularly marked. Substance P content and distribution returned to baseline by day 30 post-TNBS, although MPO activity remained slightly elevated. We concluded that TNBS ileitis is associated with a marked reduction in mucosal and submucosal substance P content in parallel with the inflammatory response. Although misoprostol attenuated granulocyte infiltration in this model, it did not prevent the disturbances in enteric substance P or mucosal protein leak.

Animals↗
PubMed1993

Development of cholinergic innervation and muscarinic receptor subtypes in piglet trachea.

We studied physiological and pharmacological maturation of cholinergic innervation to tracheal smooth muscle in piglets at three ages: < 7 days, 2-3 wk, and 10 wk. Change in tracheal tension was measured in vivo from a tracheal segment and normalized for its size. Electrical vagal stimulation induced a significantly weaker increase in tracheal tension at < 7 days when compared with 2-3 and 10 wk. In vivo studies employing vagal stimulation before and after topical application of pirenzepine (an M1 muscarinic receptor blocker) and in vitro pharmacological studies evaluating the inhibition of [3H]quinuclidinyl benzilate (QNB) binding by pirenzepine demonstrated that immature M1-receptor function could not account for the weak tracheal smooth muscle responses in the first week. Topical application of the cholinergic agonist methacholine to the tracheal segment also induced a significantly weaker contractile response at < 7 days when compared with 2-3 and 10 wk. Total density of muscarinic receptors, as well as the M1 and M3 muscarinic subtypes, was not statistically different among < 7-day-old, 1- to 3-wk-old, and adult animals. Receptor binding studies in 1-3 wk and adult animals demonstrated biphasic dose-dependent inhibition of [3H]QNB binding in tracheal smooth muscle membranes by methacholine, with a high-affinity component dependent on the availability of G protein. These high-affinity muscarinic receptors coupled to G protein were absent in < 7-day-old piglets. We speculate that the weak tracheal smooth muscle contraction observed during the first week of life is in part secondary to immature G protein function.

Administration, Topical↗
PubMed1993

Changes in resistance and ventilatory timing that accompany apnea in premature infants.

To characterize the changes in respiratory mechanics and ventilatory timing that accompany apnea in premature infants, we evaluated 36 apneas in 13 premature infants (birth weight, 1,200 +/- 350 g, postconceptional age at study 34 +/- 3 wk). Apnea was defined as a ventilatory pause > or = 10s accompanied by a decrease in heart rate of 20 beats/min. Nasal airflow was recorded with a pneumotachometer, and esophageal, pharyngeal, and nasal mask pressures were continuously measured. Inspiratory time (TI), expiratory time (TE), tidal volume (VT), and VT/TI were determined over five breaths before and after apnea. In addition, total pulmonary resistance (RT) and supraglottic resistance (Rs) were measured over the same epochs in inspiration and expiration. Before apnea, TE and RT increased (P < 0.05 and < 0.01, respectively); however, Rs did not change. Immediately after apnea, prolongation of TI occurred and both RT and Rs were increased (P < 0.01), consistent with continued upper airway instability. However, within two breaths after resolution of the apnea, RT and Rs returned to normal, reflecting rapid recovery of upper airway and total pulmonary resistance. The ventilatory changes that precede and follow apnea closely resemble those occurring during periodic breathing.

Airway Resistance↗
PubMed1993

Nitric oxide release in response to gut injury.

We evaluated nitric oxide release in several models of intestinal inflammation through luminal nitrite concentrations. In anesthetized rabbits, piglets, and guinea pigs, luminal lavages were collected from loops of normal or injured small intestine. Lavages were analyzed spectrophotometrically for nitrite (Griess reagent) and protein. Myeloperoxidase (MPO) content of intestinal segments was used as an index of granulocyte infiltration and intestinal inflammation. Acute ileal inflammation was induced by luminal acetic acid + casein in rabbits and luminal deoxycholate in neonatal piglets and adult rabbits. Chronic ileitis was induced in guinea pigs by intraluminal trinitrobenzenesulfonic acid. In each model nitrite levels in ileal lavages were significantly greater than control loops/animals. Increased luminal protein and intestinal MPO activity paralleled the changes in nitrite levels. To determine whether nitric oxide production influenced mucosal repair, segments of ileum were perfused with the L-arginine antagonist NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/ml) after acute acetic acid + casein exposure. L-NAME administration reversed the decline in epithelial permeability characteristic of epithelial restitution, causing an increase in epithelial permeability which was readily reversible. These results suggest that nitrite production is a useful index of gut injury and that nitric oxide may contribute to the functional repair of the epithelial barrier under acute conditions.

Animals↗
PubMed1993

Amelioration of chronic ileitis by nitric oxide synthase inhibition.

Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Adolescent affective aggression: an intervention model.

Affective aggression among adolescents is defined and described based upon primary research. A model of affective aggression is provided as a means of delineating the functional and observable components. Based upon these components, various interventions are provided as means of altering the aggression in adolescents.

Adolescent↗
PubMed1993

Guinea pig ileitis is attenuated by the leumedin N-(fluorenyl-9- methoxycarbonyl)-leucine (NPC 15199).

Anti-inflammatory properties have been ascribed to a series of N-(fluorenyl-9-methoxycarbonyl) amino acids called leumedins that inhibit the activity of granulocytes and T-lymphocytes. We evaluated one of these leumedins, N-(fluorenyl-9-methoxycarbonyl) leucine (NPC 15199), in a model of ileitis in guinea pigs. Ileitis was induced by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol) in anesthetized guinea pigs. NPC 15199 was administered daily (10 or 100 mg/kg, s.c.). After 7 days, the guinea pigs were anesthetized, and saline was administered intraluminally into an ileal loop created at the site of TNBS administration and was withdrawn after 30 min. The changes in lavage protein, nitrite levels, myeloperoxidase (MPO) activity and mast cell numbers were used as indices of inflammation and injury. NPC 15199 (10 or 100 mg/kg) attenuated or abolished TNBS-induced elevations in lavage protein and nitrite content. Only the high dose of NPC 15199 (100 mg/kg) attenuated ileal MPO activity and mast cell hyperplasia. Histological disturbances induced by TNBS administration included crypt hypertrophy, mucosal and submucosal fibrosis and smooth-muscle hyperplasia. These disturbances were reversed by high-dose NPC 15199 (100 mg/kg) but were minimally affected by low-dose NPC 15199 (10 mg/kg). We conclude that NPC 15199 prevents mucosal injury and dysfunction in this model of intestinal inflammation. Inhibition of granulocyte infiltration does not appear to be essential for the beneficial effects of NPC 15199 and suggests that the alternative actions of NPC 15199 may be pertinent to this model.

Animals↗