Guided tissue fabrication from periosteum using preformed biodegradable polymer scaffolds.

A successful tissue engineering method for bone replacement would imitate natural bone graft by providing the essential elements for new bone formation using synthetic scaffolds, osteogenic cell populations, and bone induction factors. This is a study of the suitability of various formulations of poly(DL-lactic-co-glycolic acid) (PLGA) foams to provide a tissue conducting scaffold in an ovine model for bone flap fabrication. Three formulations were used of different copolymer ratio and molecular weight. Porous wafers of PLGA were stacked into rectangular chambers (volume 4 cm3) enclosed on five sides. Some chambers also contained autologous morcellized bone graft (MBG). The chambers were inserted with the open face adjacent to the cambium layer of the periosteum in rib beds of seven sheep and harvested after 8 weeks in vivo. Gross and histologic examination of the resulting tissue specimens demonstrated molded units of vascularized tissue generally conforming to the shape of the chambers and firmly attached to the periosteum. Polymer degradation appeared to occur by varying degrees based on polymer formulation. New bone formation was observed only in areas containing MBG. There was no evidence of significant inflammatory reaction or local tissue damage at 8 weeks. We conclude that a PLGA foam scaffold is (1) an efficient conductor of new tissue growth but not osteoinductive, (2) contributes to the shape of molded tissue, and (3) biocompatible when used in this model. Further studies are warranted to develop practical methods to deliver bone induction factors to the system to promote osseous tissue generation throughout the synthetic scaffold.

Microsurgical replantation of the lip: a multi-institutional experience.

Traumatic amputation of the lip is a rare yet devastating event affecting both form and function. Considering the available methods for reconstruction, replantation may offer a reasonable solution. We sought to characterize the variables associated with lip replantation and to assess the outcome in a retrospective review of 13 lip replantations performed in 12 institutions utilizing a form database and clinical and photographic analysis. Lip replantation was successful in all 13 patients; partial flap loss occurred in one patient owing to iatrogenic injury. Follow-up averaged 3.1 years. Average patient age at the time of injury was 21.1 years. There were six male and seven female patients. Injuries in two patients were the result of a human bite, the remaining injuries resulted from dog bites. One patient had significant associated injuries. Average length of hospital stay was 11.9 days. Ten patients suffered amputations of the upper lip, and three suffered amputations of the lower lip. Average defect size was 10.6 cm2. Operative time averaged 5.7 hours (range 2.5 to 12 hours). Warm ischemia time averaged 2.9 hours, and cold ischemia time averaged 2.7 hours. Donor and recipient veins were often scarce; all patients had at least one arterial anastomosis, whereas no vein was available in 7 of 13 patients; vein grafts were required in one patient. Leech therapy was employed in 11 of 13 patients. Anticoagulant therapy was administered in the majority of patients. Systemic heparin was utilized in 10 of 13 patients, low molecular weight dextran was used in 7 of 13 patients, and aspirin was given to 7 of 13 patients. One bleeding complication was incurred. An average of 6.2 units of packed red blood cells was administered to 12 of 13 patients (adjusted to 250 cc/unit). Antispasmodic therapy was employed in six of eight patients intraoperatively and in two of eight patients postoperatively. Intraoperative complications included difficulty identifying veins in 7 of 13 patients, arterial spasm in 1 of 13 patients, and vessel diameter < 0.5 mm in 4 patients. Postoperatively, one patient suffered vein thrombosis requiring anastomotic revision. Broad spectrum antibiotics were administered to all patients, and there were no infections. Nearly one-third (4 of 13) patients suffered prolonged edema lasting > 4 months. Color match of the replanted lip segment was rated excellent in all cases. Hypertrophic scarring occurred in 6 of 13 patients. A total of 12 revision procedures was performed in six patients. Interestingly, leech therapy resulted in permanent visible scarring as a result of the leech bite in 6 of 11 patients treated. Ten patients demonstrated active orbicularis muscle contraction in the replanted lip segment. Stomal continence was present in all lips. Sensibility return in the replanted lip segment was quite good with 12 of 13 patients demonstrating at least protective moving two-point sensibility (> or = 10 mm). Partial replant necrosis in one patient resulted in significant scar and contraction that compromised the aesthetic appearance. Overall, however, all patients were uniformly pleased with their final results. This clinical study is one of the largest of its kind on lip replantation. Although this represents a multi-institutional experience, the data are remarkably consistent. Re-establishment of venous outflow seems to be the most problematic technical challenge. By incorporating the adjuncts of anticoagulation, leech therapy, and antispasmodics, a successful outcome can be expected despite the paucity of vessels and small vessel size. The risks of blood transfusion, lengthy operative time, and hospital stay must be weighed against the functional benefits.

Histologic changes of intraoral free skin flaps.

BACKGROUND: It was the purpose of this study to assess the histologic skin changes of free tissue transfers used to reconstruct intraoral defects. METHODS: Patients who were at least 12 months after intraoral free tissue reconstruction were selected for study. A 3-mm punch biopsy of the intraoral portion of the flap was performed and submitted for routine histologic analysis and periodic acid-Schiff (PAS) staining. The adjacent native oral mucosa was also biopsied and served as control. RESULTS: Eight patients (42 to 71 years old) were studied. A variety of skin flaps were employed and included free rectus abdominis (4), radial forearm (2), scapula (1), and osteocutaneous fibula flaps (1). Histologic examination demonstrated that all specimens maintained normal skin architecture and maturation. Adnexal structures were demonstrated in all but one. Acute inflammation in conjunction with diffuse parakeratosis and spongiosis were seen with 4 cases. Fungal forms consistent with Candida species were identified in the stratum corneum by PAS stain in these 4 cases. CONCLUSION: The histologic integrity of skin appears to be maintained in cutaneous free flaps placed intraorally. Previous studies have noted an inflammatory infiltrate in the epithelial tissues of intraorally placed flaps, yet have not commented on the significance of this finding even when it was noted in a chronic setting. Our study is the first to correlate these changes with the presence of fungi. The effect of the acute inflammation and associated fungal forms may suggest the need for chronic therapy and merits further study.

Reconstruction of the lower extremity after ablative resection for cancer.

Limb-sparing surgery for cancer of the lower extremity has ushered the development of composite, one-stage reconstructions that employ a combination of autologous tissues, bone allografts, and endoprosthetic devices. The success of these efforts in preserving limb function has been generally good, yet the ultimate level of function is less than normal. Microsurgery has assumed a progressively greater role in the reconstruction of composite defects and allows much latitude in the surgical planning and in the management of delayed complications. Although patients who opt for limb salvage reconstructions frequently require more operative procedures and have longer hospitalizations than patients undergoing primary amputation, their functional outcome surpasses that of the amputation group and thus justifies the surgical effort.

The transnasal approach to advanced lesions of the sphenoid sinus and pituitary.

The techniques of transseptal transsphenoidal hypophysectomy are discussed in detail in this article. The span of disease that may be treated by this method in addition to the need for a team approach of otolaryngologists and neurosurgeons is illustrated with several pertinent case reports.

MR of the paranasal sinuses.

The purpose of this project was to examine the anatomy and pathology of the paranasal sinuses as seen by MR imaging. This was accomplished through correlations of MR images of normal volunteers with matched cadaver whole organ cryosections. The information obtained by MRI was compared to that of plain films and CT in the detection of a variety of conditions affecting the paranasal sinuses. The majority of the pathological processes could be quite adequately imaged by T1 weighted pulsing sequences. When more tissue specific information was required in some infiltrating malignant lesions, T2 weighting pulsing sequences are quite helpful for tumors that crossed the subarachnoid space into the central nervous system or in characterizing tissues in airless sinuses. Other than the single case of osteoid osteoma where X-ray studies were superior, magnetic resonance provided equal or superior information to the X-ray examinations.

Nocturnal hypotension in older men with sleep-related breathing disorders.

Sleeping and awake blood pressures were related to sleep oxygenation and awake control of breathing in hypertensive and normotensive older men. During sleep, episodes of both hypertension and hypotension were observed, but hypotension was prominent. Five of 26 subjects exhibited episodes with a minimum mean arterial pressure of 60 mm Hg or less. These hypotensive episodes were associated with hemoglobin desaturation below 80 percent, secondary to sleep-related breathing disorders, and elevated supine nasopharyngeal airway resistance. Hypotensive subjects were habitual snorers. Waking hypertension was not associated with sleep-related breathing disorders in this older sample. In some older persons with sleep-related breathing disorders, sympathetic reflexes may be impaired, permitting hypotension and risk of circulatory failure. Epidemiologic evidence supports the hypothesis that this mechanism can explain the elevated incidence of cerebral infarction during sleep.

Effect of age on circadian rhythm of prolactin in normal men.

The 24 h secretion pattern of prolactin was studied in 9 young normal males (aged 22-46) and in 11 older normal men (aged 55-74). Despite considerably reduced duration and quality of sleep, the nocturnal surge in plasma prolactin in elderly men was the same as in young subjects. The overall 24 h secretion pattern and the absolute levels of prolactin are unaltered with age in normal men.

Circadian rhythm of plasma renin activity in older normal and essential hypertensive men: relation with inactive renin, aldosterone, cortisol and REM sleep.

The 24-h pattern of plasma renin activity (PRA), inactive renin (IR), plasma aldosterone (PA) and cortisol was studied in 13 normal men and 12 male patients with essential hypertension, all of whom were older than 55 years. Following gradual habituation over 4 days to the sleep laboratory and intravenous lines, blood samples were obtained every 2 h between 0900-2100 h and every 30 min between 2100-0900 h, during which sleep was also monitored. Plasma renin activity showed a circadian rhythm in both groups, but mean levels were lower in the hypertensive subjects (0.92 +/- 0.03 versus 1.41 +/- 0.06 ng/ml per h). The circadian rhythm of PRA in older men appeared to follow the same pattern described in younger individuals. Rapid eye movement (REM) sleep was associated with a small decrease in PRA, but this link was only evident in the normotensive group. Mean 24-h IR levels were also lower in the hypertensive group (7.26 +/- 0.18 versus 15.10 +/- 0.47 ng/ml per h) but were not affected by clock-time and generally showed no association with the 24-h PRA cycle. Mean 24-h PA was closely related to cortisol but not to PRA in both groups. Mean PA levels of the two groups were similar. Thus, the PA:PRA ratio was higher in the hypertensive group. The higher basal PA:PRA ratio in older hypertensives that emerged over the 24-h study period may reflect increased sensitivity of the adrenal gland to angiotensin II (ANG II) in hypertension of the elderly.

Dissociation of 24-hour catecholamine levels from blood pressure in older men.

Increased plasma norepinephrine levels have been observed in some persons with early essential hypertension. Although both plasma norepinephrine level and mean arterial blood pressure rise with age, little is known about the state of catecholamine secretion in elderly patients with essential hypertension. We studied the 24-hour cycle levels of plasma norepinephrine, epinephrine, and dopamine in 12 elderly hypertensive subjects and 13 age-matched normotensive controls (mean ages, 63.8 +/- 1.2 yr and 64.8 +/- 1.8 yr [SEM] respectively). Blood samples were obtained at bihourly intervals from 0900 to 2100 hours and every 30 minutes from 2100 to 0900 hours, during which time sleep and breathing were continuously monitored. A circadian rhythm was displayed in both groups by plasma epinephrine levels (mesor, 49 +/- 2 pg/ml and 38 +/- 1 pg/ml; amplitude, 15 +/- 2 pg/ml and 11 +/- 1 pg/ml; acrophase, 12.20 +/- 0.40 hr and 14.41 +/- 0.34 hr in the normotensive and hypertensive groups respectively) but not by plasma norepinephrine or dopamine levels. During the 24-hour cycle plasma epinephrine, but not norepinephrine or dopamine, levels were positively related to mean arterial blood pressure (r = 0.60 for the normotensive subjects, r = 0.57 for the hypertensive subjects, p less than 0.01 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Awake abnormalities of control of breathing and of the upper airway. Occurrence in healthy older men with nocturnal disordered breathing.

We hypothesized that preexisting diminished chemical control of breathing and narrowing of the upper airway are associated with sleep-related disordered breathing (SRDB) in healthy older men. Twenty-six subjects, aged 55 to 70, were studied. An SRDB episode was a decrease in arterial oxygen saturation (SaO2) of at least 4 percent. Some of these episodes occurred while airflow continued (ie, nonapneic episodes), and the rest occurred with apnea. Sixteen subjects had greater than 12 SRDB episodes per hour of sleep (SRDB subjects) and ten subjects had less than 8 episodes per hour (controls). During waking, the mean hypercapnic ventilatory response was lower, and the mean supine nasal airway resistance (SNAR) was higher in SRDB subjects than in control subjects. During waking, 12 of 16 SRDB subjects had one or more respiratory abnormalities: four had an elevated SNAR; four had a reduced hypercapnic response; three had a reduced hypoxic ventilatory response, and two had an abnormal flow-volume curve. Only one of ten control subjects had a respiratory abnormality (an elevated SNAR). Also, the number of SRDB episodes per hour correlated with the SNAR, and the minimum SaO2 during sleep correlated with the magnitude of the hypercapnic response. We conclude that SRDB occurs commonly in otherwise healthy older men with preexisting abnormalities of control of breathing or of the upper airway.

Sleep related breathing disorders in older men: a search for underlying mechanisms.

The incidence of sleep-related breathing disorders (SRBDs) associated with hemoglobin desaturation was determined by nocturnal polygraphic evaluations in 26 healthy men, aged 55-70 years. Sixteen subjects (62%) had abnormal rates of at least 12 episodes per hour of sleep: 8 had occlusive, and 8 had central apnea or hypopnea. During waking ten of 16 SRBD subjects and only one subject without SRBDs exhibited either an elevated nasopharyngeal airway resistance (n = 4) or a reduced ventilatory response to hypercapnia (n = 4) and/or hypoxia (n = 3). However, these abnormalities were not related to the type or severity of SRBDs, and 6 subjects with SRBDs demonstrated no respiratory defect. We conclude that SRBDs have a very high incidence in older males and are not usually secondary to pulmonary cardiac, neurological, or behavioral disorders. Additionally, we hypothesize that abnormalities in ventilatory control or upper airway resistance contribute to SRBDs, but depression of brain stem reticular formation activity during sleep plays a primary role in these disorders. Factors related to both aging and SRBDs are reviewed. These include reduced chemoreceptor responses, altered steroid hormone metabolism, and use and metabolism of hypnotic drugs and alcohol.