[Results of selective proximal vagotomy after 13 years]. This study reports the long-term results of 216 patients after highly selective vagotomy (HSV) for duodenal ulcers operated from 1970 through 1978 with a mean follow-up of 12.8 years (8.3-15). 26 patients developed symptomatic ulcer recurrences (12%) within 4 to 135 months following surgery, the cumulative recurrence rate (Kaplan-Meier) at 13 years was 20.3%. Acidity analyses showed a postoperative mean reduction of basal acid output (BAO) and maximal acid output (MAO) values of 80.7% and 74.8% respectively with no differences according to recurrences. The risk of recurrence was similar for duodenal (22/194) and pyloric ulcers (4/22) and no differences were found with respect to sex, additional drainage procedure, smoking habits, acute or elective operation and first or recurrent ulcers. Risk was slightly higher for complicated ulcers (p less than or equal to 0.07), but without reaching statistical significance. 78.5% of patients showed (very) good results (Visick I or II), only 6% were Visick III. HSV is therefore regarded as a valuable therapeutic measure for the treatment of duodenal ulcer independent of patient compliance.


[Preventive or therapeutic parathyroidectomy in primary hyperparathyroidism]. The only causal treatment of primary hyperparathyroidism (PHPT) is parathyroidectomy. There are indications in the literature that despite operation expectation of life is shortened because of an increased frequency of cardiovascular and malignant diseases leading to the recommendation for early surgery even in uncomplicated PHPT. It is easier to convince an asymptomatic patient of an operation when he is informed about complications and consequences of an expectative attitude. Therefore, we reviewed our 71 patients operated upon during a 4-year-interval, 58 of whom were followed-up. During 82 operations 115 pathologically altered parathyroid glands were removed. Two persistent paralyses of the recurrent nerve occurred, however, without alteration of the voice. Follow-up of 82% of patients revealed 2 cases of recurrent nephrolithiasis (1 hypercalcaemia, 1 normocalcaemia). Three (5%) true recurrences were found, but neither a pancreatitis nor a peptic ulcer was noted during long-term follow-up. None of the 137 patients operated for a bleeding or perforated peptic ulcer during the last 10 years and 1 of 55 patients with acute pancreatitis during the past 8 years suffered from a PH-PT. However, morbidity and mortality of these two conditions was high. Although correlation to PHPT was low we recommend early operation of PHPT because of the low morbidity rate, zero lethality and reduced expectation of life.


[Endoscopic therapy of benign anastomotic stenoses in the area of the colon and rectum by electro-incision and balloon dilatation]. 21 patients with a severe anastomotic stenosis in the colorectal region were treated with hydraulic balloon dilatation and endoscopic electro-incision. The severity of symptoms directly correlates with the extent of stenosis (degree I phi 13 mm, n = 12; degree II phi 7 mm, n = 6; degree III phi 4 mm, n = 3). All patients with a stenosis of degree I and II were symptom-free after the endoscopic therapy. In 2 of 3 cases the symptoms of stenosis of degree III could clinically be improved after the treatment. The average frequency of dilatation was 1.5 x, complications such as bleeding or perforation were not registered. Animal studies explain anastomotic stenosis through an increased submucosal formation of collagen fibers followed by formation of scars in the anastomosis. The efficiency of electro-incision and balloon dilatation is based on an increased diameter in the anastomotic region without increased formation of new collagen fibers.


[Anterior and posterior rectopexy with levator repair in patients with rectal prolapse and incontinence]. A prospective clinical, manometric and radiological study has been performed, before and after rectopexy, on 18 female patients with complete rectal prolapse, and varying degrees of incontinence. All patients, mean age 62 years, underwent anterior-posterior fixation (Ivalon or Vicryl) of the rectum with posterior pelvic repair of the puborectalis muscle. 13 patients with obstipation and rectal prolapse were treated by rectopexy combined with sigmoidectomy. Postoperatively there was a significant increase in the resting anal pressure and maximum voluntary contraction pressure (p = 0.01). Continence was improved in 16 patients (89 percent), 9 (56 percent) of whom regained normal continence. No significant change in pelvic descent or anorectal angle was seen postoperatively. Following abdominal rectopexy and resection obstipation was reduced in 9 of 13 patients (70 percent).


Interbody fusion of the lower cervical spine: a dangerous surgical method? Our follow-up study of 175 cases of interbody fusion of the lower cervical spine was conducted to show the complications that occurred in our department with what is considered to be a tried and tested method. From 1976 to 1990, 175 patients were treated with this method. These 175 cases included 150 fractures and/or dislocations. The indications for surgery in the remaining 25 cases were tumors and metastases, inflammatory or degenerative diseases and chronic instabilities following laminectomy. The following complications were seen: 4 cases of infection, 3 postoperative redislocations, 2 cases of extensive loosening of metal, 1 unilateral lesion of the vertebral artery, 1 nonunion with plate fracture, 1 post-operative radicular disorder in an otherwise neurologically normal patients, and 1 secondary extension of the interbody fusion required after failure to recognize a two-segment lesion.


[Resection of esophageal cancer without thoracotomy by manual dissection and eversion stripping]. At the department of surgery of the university of Cologne-Lindenthal, 184 patients (142 with squamous cell carcinoma of the esophagus, 42 with adenocarcinoma of the gastroesophageal junction) underwent blunt dissection of esophageal cancer between 1983 and 1991. Tumor expansion classified by the pathologist was stage I in 13.6%, stage II in 31.0%, stage III in 41.8%, and stage IV in 13.6% of all cases. Histological tumor differentiation was graded well in 4.3%, moderate in 71.7%, and poor in 19.6%. Principally a gastric tube was used for esophageal replacement (96.3%), while interposition of the large bowel was performed in 5 cases. All the patients were prospectively monitored for perioperative complications. 64.7% fared without any complications intraoperatively. The most frequent intraoperative complications were damage of the pleura parietalis (16.3%), rupture of the tumor during dissection (13.0%), and lesion of the spleen (11.4%). 29.9% of the patients had a postoperative course without any complications. Pleural effusion (38.6%) and insufficiency of the cervical anastomosis (22.8%) were the most frequent complications seen postoperatively. Hospital mortality amounted to 6.0%. Six months after the operation most patients deemed their quality of life satisfying or excellent, respectively. The cumulative survival rate (without hospital mortality) was 78.3% after the first year, 24.7% after the third year and 20.6% after the fifth year.


[Holmium:YAG and erbium:YAG infrared laser osteotomy]. The in-vivo bone ablation characteristics of a pulsed solid-state erbium:YAG laser were compared to those of a pulsed solid-state holmium:YAG laser. Partial osteotomies in the maxillary, the mandibulary, and the nasal bones of white rats were performed. The tissue response was examined by light microscopy. Thermal gradients following the laser application were also measured. Over all energy levels tested the erbium:YAG laser produced ablation of bone with minimal thermal damage to the adjacent tissue. The results of this study are promising for future application of the infrared holmium- and erbium:YAG lasers in otorhinolaryngology.


[Treatment of peritonitis with staged lavage: prognostic criteria and course of treatment]. In order to define rational criteria for "planned relaparotomies" (PR) in the treatment of critical intra-abdominal infections we have analysed characteristics and the clinical course of 377 patients with diffuse peritonitis 152 of whom were treated by PR. More detailed prognostic aspects and data of the clinical course were prospectively investigated in 111 cases. Patient's age and an underlying malignoma revealed to be of prognostic significance in both univariate and multivariate analysis. The number of organs involved in septic organ failure during the treatment was a further indicator of risk. 40% of our patients, however, survived even an impairment of 5 organ-systems. The successful eradication of the source of peritonitis either with the 1st operation or only with consecutive operations resulted in a crucial difference of the mortality rate with 14% and 64% respectively. The failure to accomplish a definite operative resolution was accompanied by a mortality rate of 90%. The systematical application of PR facilitated control and completion of the eradication of the source of peritonitis. In one third of the patients treated by PR this technique led to early detection of relevant complications and adequate operative treatment. Patients in whom primarily a definitive eradication of the source of peritonitis had been accomplished did not benefit from PR. In patients with persisting or relapsing peritonitis, however, PR was accompanied by a 27% reduction of mortality.


[Consequences of routine gastroscopy before cholecystectomy]. In a retrospective study of 610 patients the role of routine gastroscopy prior to cholecystectomy was investigated. The results demonstrated that only in a low incidence (11% of patients gastroscopied) relevant findings are present. However, most of these patients had a typical history. Therefore, despite risks, routine preoperative endoscopy prior to cholecystectomy should be performed only in patients with a history of upper abdominal pain or discomfort.


Posttympanostomy otorrhea: the efficacy of canal preparation. Otorrhea is the most common posttympanostomy complication. This study is designed to determine the efficacy of canal preparation prior to tympanostomy tube placement. One hundred thirty ears were prospectively randomized into prepared (Betadine and alcohol) and nonprepared (control) groups. Cultures obtained before, during, and after preparation were analyzed to determine the external canal flora and effectiveness of sterilization. Prepared ears and nonprepared control ears were examined for relation to otorrhea. Forty percent of the canals were sterile before preparation, and only 8% harbored suspected pathogenic organisms. Canal preparation successfully sterilized only 33% of the ears that contained bacteria. There was no difference in the otorrhea incidence among treatment groups (9.8%). Based on these bacteriologic and clinical findings, it is concluded that canal preparation with Betadine and alcohol does not reduce posttympanostomy otorrhea.


Analysis of the efficiency of retrocochlear screening. The auditory brainstem response (ABR), as well as associated audiologic and radiographic studies of 175 patients suspected of having cerebellopontine angle tumors were reviewed. The majority of patients presented with asymmetric hearing loss. Eight acoustic neuromas were identified. All eight had abnormal ABRs. The false-positive rate was 22%. Rollover and acoustic reflex testing played a minimal role in the decision as to whether or not an ABR was ordered and, as a result, are not important in the search for retrocochlear disease. The cost per tumor diagnosed was roughly $7600. A rational approach to tumor screening based on the efficiency and cost of the screening tests, the frequency of abnormal ABRs, and the cost per tumor diagnosed is presented.


H-Index: a new measure of glottal efficiency for the pathologic voice. Taking advantage of the extended dynamic range of digital analysis of voice the H-Index represents the first proposed acoustical measure of glottal efficiency. "Hi" /hai/ was chosen to evaluate glottal efficiency since it provides an excellent test of glottal transformation from voiceless to voiced sound energy, the upper vocal tract having a neutral effect. Fifteen individuals with normal voices and 30 patients with hoarse voices were asked to say "hi." The power ratio of /h/ to /a/ was calculated from peak power of each measure from the power envelope. Voice quality had a highly significant effect on measured values (P < .001). A high degree of correlation (P < .001) was found with the AC/DC ratio, a standard aerodynamic measure of glottal efficiency. The results indicate that the H-Index represents an excellent measure of glottal efficiency, obviating the need of invasive techniques or expensive, highly specialized equipment.


Time series analysis of glottal airflow in normal and pathological phonation. Time series analysis of glottal airflow was carried out on 26 normal controls and 40 patients with voice disorders, using a modification of Isshiki's original technique which uses a hot-wire flowmeter, taking cycle-by-cycle fluctuations into consideration. The mean flow rate and mean AC/DC were shown to have significant differences among normal and patient groups. The standard deviations of AC/DC and AC/DC perturbation were calculated from the AC/DC value of 50 cycles and shown not to vary significantly among the normal and patient groups. The relationship between AC/DC and perceptual impression of voice was also studied among 20 selected patients with breathy voices. Using Spearman's rank correlation coefficient, this relationship was found to have statistical significance (P < .05).


Treatment of hemangiomas of the head and neck. Hemangiomas are a group of pediatric tumors that present at or soon after birth. Rapid proliferation is seen in the neonatal period, and may continue for the first year of life. Involution follows, and may last as long as 12 years. Since hemangiomas invariably involute, the vast majority have been left untreated. At least 10% to 20% of cases, however, will need active intervention, traditionally in the form of oral Prednisone. The frequent occurrence of life-threatening complications, permanent deformities, and irreversible psychosocial damage in spite of adequate steroid therapy necessitated a fresh look at the management of these lesions. Using recently developed laser technology alone or in combination with surgical excision, the authors have developed guidelines for safe intervention in all stages of the hemangioma cycle. Safe, active intervention in accordance with these guidelines offers an alternative to the more conservative approach previously advocated.


The effect of unilateral and bilateral nasal obstruction on snoring and sleep apnea. The purpose of this study was to compare apnea and snoring in patients with different patterns of nasal resistance: normal, high unilateral, and high bilateral. The authors examined 683 unselected patients referred for evaluation of snoring and possible sleep apnea. All patients had determination of nasal resistance (performed during wakefulness in the seated posture) and nocturnal polysomnography including quantitative measurement of snoring. Analysis of variance showed no significant difference in apnea and snoring indices among the three nasal resistance groups (normal, high unilateral, and high bilateral). Furthermore, there was no significant difference in the frequency of patients with different severity of apnea and snoring among the three groups. It is concluded that 1. unilateral and bilateral elevation of nasal resistance may lead to equally severe snoring or apnea; 2. there is no direct relationship between awake seated nasal resistance measurement and sleep disordered breathing; and 3. measurements of supine nasal resistance during sleep may be required to elucidate the relationship between sleep-disordered breathing and nasal obstruction.


Preservation of hearing and facial nerve function in resection of acoustic neuroma. The surgical results in 78 recent cases of total removal of unilateral acoustic neuroma in which an attempt was made to preserve cochlear function have been added to the authors' previous series of 66 cases to evaluate the factors influencing the ability to preserve useful hearing. Useful hearing was defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%. Analysis using a logistic regression model showed that certain preoperative clinical parameters such as tumor size, speech discrimination score, and gender were significantly correlated with hearing outcome. Favorable outcome was significantly correlated with smaller tumor size, higher preoperative speech discrimination score, and male sex. From this data, an explicit formula was devised for predicting hearing outcome for an individual patient. In four cases with useful hearing preserved, there was improvement of greater than 15 percentage points in speech discrimination scores. While preoperative auditory brainstem responses were not predictive of hearing preservation, monitoring of intraoperative auditory evoked potentials was predictive of hearing outcome in selected cases. Specifically, when wave V was unchanged at the end of the operation, even if it may have been transiently lost during surgery, useful hearing was invariably preserved.


Three-dimensional surgical anatomy for stapes surgery computer-aided reconstruction and measurement. To define anatomical relationships relevant to stapes surgery, computer-aided three-dimensional reconstruction and measurement were performed on nine normal temporal bones. The mean distance from the inferior portion of the long process of the incus to the center of the oval window was 3.80 mm. The shortest distance from the center of the oval window to the utricular macula, saccular membrane, and macula averaged 1.37, 1.60, and 2.13 mm. Surgery directed posteromedial-superior from the oval window was found to be most dangerous because it would come so close to the utricular macula; a posteromedial-inferior approach was found to be safest. The distance from the inferior margin of the oval window inferiorly to the cochlear duct in the hook portion ranged between 0.58 and 1.29 mm, suggesting that when a drill hole is made on the inferior margin of the oval window to lift up a depressed stapes footplate, the hole should not be greater than 0.5 mm in diameter.


Some forms of tinnitus may involve the extralemniscal auditory pathway. It has previously been shown that the click-evoked responses recorded from the intracranial portion of the eighth nerve in patients with incapacitating tinnitus are not abnormal, nor is the latency of peak III of the click-evoked brainstem auditory-evoked potentials significantly altered; however, the latency of peak V is slightly (but significantly) shortened in comparison to that of patients with the same degree of hearing loss but no tinnitus. In this study the hypothesis that the extralemniscal auditory system is involved in the generation of tinnitus is tested. We made use of the fact that neurons of the extralemniscal auditory system also receive input from the somatosensory system, and that stimulation of the somatosensory system can influence the processing of auditory information in the extralemniscal system. In 4 of 26 patients with mild-to-severe tinnitus whose median nerve was stimulated electrically, the tinnitus increased noticeably during stimulation, in 6 the intensity of the tinnitus decreased noticeably, and in the remaining 16 there was no noticeable change in the tinnitus. In some of the patients the character of the tinnitus changed in a complex way. There were no significant differences in hearing thresholds in these three groups of patients. Electrical stimulation of the median nerve in 12 individuals with normal hearing who did not have tinnitus either had no effect on the loudness of sounds or it caused a slight increase in the loudness.


Facial nerve to facial canal cross-sectional area ratio in children. The incidence of facial palsy among children is lower than that among adults, and the recovery rate after facial palsy among children is higher than that of adults. To investigate these differences, we compared the cross-sectional area ratio of the facial nerve to that of the facial canal in 26 pediatric temporal bone specimens with that of 10 adult temporal bone specimens. The ratios were 0.31 +/- 0.08, 0.35 +/- 0.10, and 0.18 +/- 0.12, respectively, in the labyrinthine, horizontal, and mastoid segments of pediatric specimens. The ratios for adult specimens were 0.46 +/- 0.07, 0.52 +/- 0.17, and 0.37 +/- 0.04, respectively, in the labyrinthine, horizontal, and mastoid segments. These ratios were all significantly smaller than those for the corresponding segments of the adult specimens (P < .01). The results indicate that in children there is less possibility for entrapment of the facial nerve in the facial canal, and that children require facial nerve decompression less often than adults.


Defect reconstruction and cerebrospinal fluid management in neurotologic skull base tumors with intracranial extension. Intracranial extension (ICE) is the spread of tumor into the subarachnoid space through dura or along cranial nerve roots. The single-stage removal of the skull base tumor with its ICE has been confounded by cerebrospinal fluid management and defect reconstruction. The purpose of this report is to review a current protocol for managing the cranial base tumor and its ICE as a unit. The ventricular shunting paper of 1987 is retracted. All tumors were managed at a single stage. Defect reconstruction was size dependent. Ninety-eight neurotologic skull base tumors with ICE were managed from 1971 to 1991. The new protocol was initiated in 1987. Results specific to this group are highlighted. For glomus tumors, cerebrospinal fluid leak rates have been dramatically reduced overall from 14.5% to 4%. The leak rates for nonglomus tumors, overall, have improved slightly. Complications are discussed. The development of this surgical approach protocol improves the functional outcome in patients of surgeons who aspire to disease "cure" rather than "control."


Frontal sinus fractures in the pediatric population. Full development of the frontal sinus is not achieved until approximately 19 years of age. An evaluation of frontal sinus injuries isolated to the subset of patients less than 20 years old has yet to be reported. In order to determine whether age was a factor in the clinical course of patients with frontal sinus fractures, 209 patients who sustained frontal sinus fractures from January 1985 to April 1990 were identified using the trauma registry from all six major trauma centers, one of which is a pediatric trauma center, in a county of 2.5 million people. Forty patients (19%) were between the ages of 6 and 19 years at the time of their injury. Computed tomography imaging of these pediatric patients identified associated head and neck fractures in 37 (93%) as well as significant central nervous system injury in 22 (55%). Seventeen pediatric patients were treated nonoperatively and 1 died prior to the planned surgery. A detailed analysis of extent of injury and treatment together with a comparison of the 169 adult and the 40 pediatric patients is presented.


Electrical promontory stimulation in patients with intact cochlear nerve and anacusis following acoustic neuroma surgery. Anacusis following hearing preservation surgery for acoustic neuroma removal in which the cochlear nerve was preserved has been explained on the basis of neural or vascular compromise. In the absence of pathologic evidence for either theory, a physiologic model was chosen. Electrical promontory stimulation with monitoring of subjective and electrically evoked auditory brainstem responses was undertaken. A positive response to stimulation suggests a vascular impairment of the cochlea sparing the cochlear nerve and spiral ganglion. The absence of response suggests loss of neural integrity at the level of the spiral ganglion or cochlear nerve. Six patients who suffered anacusis following hearing preservation surgery for acoustic neuroma were studied. Data regarding electrical promontory stimulation, auditory brainstem responses, and implications of the possible role of cochlear implantation are discussed.


Temporal bone histopathology in chronically infected ears with intact and perforated tympanic membranes. Chronic suppurative otitis media has been clinically defined as a chronic discharge from the middle ear in the presence of a perforation of the tympanic membrane. However, irreversible tissue pathology in the middle ear or mastoid can occur behind an intact tympanic membrane. One hundred forty-four human temporal bones with chronic otitis media were divided into two groups: those with perforated (28) and those with nonperforated (116) tympanic membranes. The histopathological findings of their middle ears were compared. Granulation tissue in various degrees was the most prominent pathological feature. It was observed in 96% of temporal bones with perforation of the tympanic membrane, and in 97% of those without perforation. Also found were ossicular bony changes (96% with perforation; 90.5% without), middle ear effusion (93% with perforation; 89% without), cholesterol granuloma (21% with perforation; 12% without), cholesteatoma (36% with perforation; 4% without), and tympanosclerosis (43% with perforation; 20% without). This study shows that the histopathological changes of the middle ear are similar in temporal bones with and without perforation of the tympanic membrane. The clinician should, therefore, be aware that an intact tympanic membrane does not necessarily preclude the presence of gross pathological changes of the middle ear cleft.


A canine model for studying laryngospasm and its prevention. Laryngospasm, if prolonged, can result in serious sequelae due to the lack of a uniformly effective treatment. Prevention, therefore, through pharmacologic intervention, is an attractive concept. In order to study the effects of various drugs in preventing laryngospasm, a reliable animal model capable of producing sequential, repetitive episodes of laryngospasm is necessary. In this study, the canine model of laryngospasm previously described by Aviv, et al. was modified to overcome technical factors which limited its use in this regard. Details of the technique and the results from eight animals will be presented. Results in two animals with the use of prophylactic topical lidocaine will also be discussed. The reliability and reproducibility of this model make it ideal for the study of laryngospasm and open the way for investigation into its prevention.


Sucralfate in alleviating post-tonsillectomy pain. Tonsillectomy results in severe throat pain, ear pain, and trismus until the exposed and inflamed muscle becomes covered with regenerated mucosa. Sucralfate binds with the fibrinous exudate of duodenal ulcers, forming a protective barrier that promotes healing. If a similar buffer could be created in the tonsillar bed, morbidity may be diminished. A double-blind, randomized study was completed in 34 adult patients to determine whether sucralfate, given four times daily for 10 days as a swish and swallow, would significantly reduce postoperative pain and promote healing and recovery. Sucralfate significantly lowered postoperative throat pain, otalgia, and trismus. Sucralfate is a safe and well-tolerated topical agent that offers significant pain reduction and may promote healing in tonsillectomy patients.


Association of skull base and facial fractures. A retrospective analysis of 268 trauma patients with facial fractures who received computed tomography of the head was undertaken to assess an association with skull base fractures. The incidence of skull base fracture was compared to facial fractures of various anatomic locations. Skull base fractures were significantly increased in orbital wall/rim fractures (36.0%, P = .0823). In contrast, skull base fractures related to orbital floor (27.3%, P = .6191) and maxillary/zygomatic (29.4%, P = .1148) fractures were not significantly greater and were infrequently seen with mandible (4.0%, P = .0454) and nasal (7.7%, P = .0345) fractures. The incidence of skull base fracture was directly associated with the number of facial fractures per patient; one facial fracture (21.0%), two facial fractures (30.4%), and three or more facial fractures (33.3%) (P < .05). The incidence of skull base fractures was related to the location of facial fractures and the number of facial fractures per patient. The results provide additional clinical information to facilitate the prompt detection and diagnoses of skull base fracture.


Infant botulism: considerations for airway management. Infant botulism is a national problem with over 1000 confirmed cases in the United States since it was first recognized as a distinct clinical entity in 1976. The disease is characterized by a progressive, symmetrical descending paralysis of cranial nerves with eventual involvement of axial and trunk muscle innervation. Most infants progress to complete respiratory failure. An initial report in 1979 recommended early tracheotomy for avoidance of long-term intubation complications. However, over the past 10 years at St. Christopher's Hospital for Children, analysis of airway management in 11 patients with infant botulism revealed a median intubation time of 16 days. Following extubation, all patients progressed to complete respiratory recovery without adverse laryngotracheal sequelae. Otolaryngologists consulted for the airway management of infants with botulism should adopt a conservative approach with meticulous monitoring of endotracheal tube sizes and leak pressures. Tracheotomy is rarely required.


The electrophysiologic and histologic effects of the Argon Beam Coagulator on peripheral nerves. The electrophysiologic and histologic effects of the Bard Argon Beam Coagulator (ABC) were investigated in the New Zealand White rabbit. Thirty-four rabbits were divided into three groups. Controls underwent simple femoral exploration and closure. The remaining rabbits' femoral nerves were spot coagulated with either the ABC or standard electrosurgical unit (ESU). Stimulus thresholds were recorded before treatment and again prior to sacrifice at 0, 30, 60, or 120 days. Thresholds were significantly elevated for the ABC and ESU compared to controls (P = .0077 and .0351, respectively). Changes in threshold were greater for the ABC than for the ESU, but were not significant. All ABC- and ESU-treated nerves had significant histologic injury when compared to controls (P < .0002). Although the ABC may be clinically safe, significant injury to rabbit femoral nerves occurs when they are exposed to energy emitted by this instrument.


Vincristine-induced recurrent laryngeal nerve paralysis. Vincristine-sulfate-related vocal cord paralysis has been reported infrequently in the literature. The neurotoxicity of the vinca alkaloids is well-known; however, the potential for cranial nerve involvement is not widely recognized. Given the complexity of the typical patient receiving such a chemotherapeutic agent, the potential for misdiagnosis is high. Many patients have primary tumors or metastatic lesions in sites that could cause the clinician to overlook this reversible cause of neurologic dysfunction. This study describes the first three reported pediatric cases of vincristine-induced vocal cord paralysis. Two patients developed increasing stridor secondary to bilateral vocal cord paralysis; the third developed a unilateral vocal cord paralysis. All resolved spontaneously upon withdrawal of the vincristine. Vinca-alkaloid-induced vocal cord paralysis is a potentially dangerous but reversible lesion. Otolaryngologists should be aware of the association between these agents and cranial nerve neuropathies.


Anatomic correlates of normal and diseased adenoids in children. In order to better understand the pathogenesis and sequelae of obstructive adenoid hyperplasia in children, the anatomic relationships of the adenoids to the hard and soft palates, oropharynx, and nasopharynx were studied in vivo in 94 children. Direct, intraoperative palatal, nasopharyngeal, and oropharyngeal measurements were performed in 19 children with normal, nondiseased adenoids (controls [C]) and compared to 75 children undergoing adenoidectomy for obstructive adenoid hyperplasia (OAH) (n = 44) or chronic adenoid infection (CAI) (n = 31). As expected, the weight and volume of the adenoids removed were significantly greater in the OAH vs. CAI group (P < .001). Before adenoidectomy, the volume of the nasopharynx was significantly smaller in the OAH group; however, nasopharyngeal volumes after adenoidectomy were quite similar in all three groups and ranged from 5.4 to 6.2 cc. Only the change in the volume of the nasopharynx after adenoidectomy for obstruction was significant (2.5 +/- 1.2 cc, P < .01). Differences in oropharyngeal and palatal dimensions were not associated with longstanding obstruction from adenoid hyperplasia. These data indicate that the nasal obstruction from adenoid hyperplasia is due to an absolute increase in adenoid size rather than a relatively smaller nasopharynx. Differences in palatal and oropharyngeal dimensions usually described and attributed to longstanding nasal obstruction could not be demonstrated in this study.


Continuous pressure measurements in the pharynx and esophagus during sleep in patients with obstructive sleep apnea syndrome. Pressure measurements were made preoperatively at six sites in the pharynx and esophagus in 18 obstructive sleep apnea syndrome (OSAS) patients, 3 social snorers, and 6 healthy normal controls. Repeat measurements were made approximately 2 months after uvulopalatopharyngoglossoplasty (UPPGP) in 10 of the OSAS patients. The pressure transducers were contained in a thin silicone tube inserted through one nostril, and measurements were made both in the awake state and throughout a night's sleep. Oxygen saturation was also continuously recorded and, additionally, nasal and oral airflow measurements were made as the postoperative control. The majority of patients had obstruction in more than one pharyngeal segment, and the site(s) of obstruction differed in the awake and sleeping states. After UPPGP, 3 of the patients had neither subjective nor objective evidence of obstruction, while the remaining 7, although subjectively improved, had varying degrees of residual obstruction in the nasopharynx and at the level of the soft palate.


Relationship of chronic ethmoidal sinusitis, maxillary sinusitis, and ostial permeability controlled by sinusomanometry: statistical study. Three hundred sixty-seven successive patients suffering from chronic maxillary sinusitis (CMS) were thoroughly examined by means of maxillary sinusoscopy, a CT scan of the facial sinuses, and sinusomanometry (SMM). Ninety-eight cases of unilateral CMS, 269 cases of bilateral CMS, and 444 chronic ethmoidal sinusitis (CES) cases were evaluated. According to SMM, the maxillary ostia were divided into two groups: 1. maxillary ostium patency (MOP) group and 2. the maxillary ostium nonpatency (MONP) group. The unilateral and bilateral pathologies were separately analyzed so as to minimize the effects of general or systemic causes on the results. MONP is, in both bilateral and unilateral groups, significantly linked with the presence of ethmoidal sinusitis (P < 10(-6); P = .026), while the correlation between MOP and the ethmoid status does not appear to be significant in either group. Thus, there seems to be a close relationship between CES and maxillary ostial dyspermeability in cases of CMS.


The microsurgical anatomy of the abducens nerve in its intracranial course. The microsurgical anatomy of the abducens nerve through its intracranial course was studied in 20 specimens obtained from 10 cadaver heads fixed in formalin. Another 20 specimens were used to study the pattern of branching of the nerve trunk. The following intracranial segments were studied: subarachnoid or intracisternal, petroclival, and intracavernous. Angulations, neurovascular relationships, and branching patterns of the nerve are described. The long intracranial course of the abducens nerve, its tortuosity, and its tight attachment to the skull base at the level of the petrous apex may influence its vulnerability in some pathological conditions.


Electrically evoked auditory brainstem response monitoring of auditory brainstem implant integrity during facial nerve tumor surgery. Evoked potentials identified as electrically evoked auditory brainstem responses (EABRs) have been recorded from a patient in response to electrical stimulation of the cochlear nucleus via an auditory brainstem implant. Recording such EABRs during surgery for removal of an ipsilateral facial nerve tumor provided a means to monitor the integrity of the implant. The presence of stable EABRs similar to those obtained before surgery indicated that the lead wires had not been severed and that the implanted electrodes had not been dislodged. EABR recording may also be useful for assisting with positioning the stimulating electrodes during initial implantation surgery, by verifying that stimulation can activate the auditory system.


Ventricular dysphonia: a profile of 40 cases. Ventricular dysphonia is a poorly understood disorder involving ventricular fold participation during phonation. A population of ventricular dysphonia patients was evaluated using phonatory function studies such as laryngovideostroboscopy, advanced acoustic analysis, and electroglottography to identify shared epidemiologic characteristics and to discuss possible neuromuscular mechanisms and causes. Forty patients with ventricular dysphonia were studied and epidemiologic, acoustic, and histologic data were analyzed. In almost all cases, the authors found abnormalities affecting the glottis caused by a related medical condition. The abnormalities included true vocal cord (TVC) aperiodicity in 100% of the patients, TVC asymmetry in 65%, a laryngeal mass or foreign body (usually Teflon) in 35%, TVC erythema or edema in 32.5%, and TVC bowing in 22.5%. Ventricular dysphonia seems to be primarily a compensatory mechanism for glottic dysfunction. Therapy is based on identifying and correcting the underlying abnormalities. Laryngovideostroboscopy is a particularly important tool in examining chronic dysphonia.


Laser etching of teeth for orthodontic bracket placement: a preliminary clinical study. Current interest in the use of layers in clinical dentistry has suggested that this technique may be applicable to enamel etching in orthodontics. A pulsed Nd:YAG laser was used to etch the enamel surfaces of teeth in vivo prior to the bonding of orthodontic brackets with composite resin. Overall laser bonding took considerably longer, was less reliable in terms of bond strength, and produced more discomfort than conventional acid etching. The use of the ND:YAG laser for etching teeth prior to bonding orthodontic brackets is not recommended.


Effect of the ArF excimer laser on human enamel. Human enamel surface was irradiated with ArF excimer laser and examined under light microscopy and scanning electron microscopy (SEM). Enamel surface was irradiated at three different areas with different energy fluences. It is demonstrated that the ArF excimer laser causes ablation of the calcified hard enamel tissue. Ablation curves were measured. There was no significant difference found in the etch depth between the three different areas of enamel surface. The morphology of the irradiated areas seen under the SEM was found to be dependent on energy fluence. It changed with increase in energy fluence from being etched to forming a smooth, fused, glaze-like surface and then at very high energy fluences producing a rough surface. The influence of the laser irradiation was confined to the irradiated area only, with no visible heat damage to the surroundings. These results suggest that excimer laser could be applied in a controlled and defined manner for tooth enamel treatments in dentistry.


Endoscopic laser therapy of the watermelon stomach. Endoscopic laser therapy has been used in the treatment of vascular lesions throughout the gastrointestinal tract. The "watermelon stomach" is a pattern of vascular ectasia in the gastric antrum that results in chronic gastrointestinal blood loss and iron deficiency anemia. We have treated 7 transfusion dependent patients with a watermelon stomach using endoscopic laser therapy. Four of these patients were treated with the argon laser and 3 with the Nd:YAG laser. Patient age and prior transfusion requirements were similar in both groups. The mean number of treatments to obliterate vascular lesions and eliminate the need for transfusions was 5.75 +/- 0.89 (SEM) for the argon laser and 2.33 +/- 0.27 for the Nd:YAG laser (P < 0.05). Lesions recurred and required retreatment in 1 patient treated with the Nd:YAG laser and 3 patients treated with the argon laser (mean follow-up of 35 months). We conclude that endoscopic laser therapy with either the argon or Nd:YAG laser is an effective treatment modality for antral vascular ectasia (watermelon stomach). The Nd:YAG laser requires fewer treatment sessions than the argon laser to obliterate the lesions without increased risk of complications.


Treatment of distal ureteral tumors using endoscopic argon photoirradiation. This is the first report on the use of endoscopic argon photoirradiation to treat patients with low-grade ureteral tumors involving the distal ureter. Using a rigid ureteropyeloscope, a 300 mu or 600 mu quartz fiber, and 5 watts (W) of power in a continuous-wave mode, the lesions were ablated without complication. Patients remain free of ureteral recurrence after 5, 7, and 22 months. We conclude that the shallow (1 mm) depth of penetration and the ability to use the fiber in either a contact or noncontact mode provide the surgeon a large margin of safety and low risk of ureteral perforation.


Effect of aspirin on photodynamic therapy utilizing chloroaluminum sulfonated phthalocyanine (CASP). The efficacy of photodynamic therapy (PDT) is mediated through a direct vascular effect. Interference with platelet function and resulting vascular stasis have been recently demonstrated utilizing the photosensitizer dihematoporphyrin ether (DHE). We examined the effect of aspirin, a known inhibitor of both cyclooxygenase and platelet activity, on PDT using chloroaluminum sulfonated phthalocyanine (CASP). Thirty-six rats implanted with a window chamber were given either 0.1 mg/kg (low dose) or 10 mg/kg (high dose) aspirin immediately before, immediately after, or 6 hours after the completion of CASP-PDT. Aspirin in either dosage did not appear to have any effect on the window vasculature when given immediately after light exposure. A moderate inhibition of vascular response was seen in animals treated with aspirin pre-PDT, whereas high-dose aspirin completely abrogated the CASP-PDT vascular response when given 6 hours post-PDT. These data indicate that aspirin can effect CASP-PDT in both time-dependent and dose-dependent fashions.


Changes in type I collagen following laser welding. Selection of ideal laser parameters for tissue welding is inhibited by poor understanding of the mechanism. We investigated structural changes in collagen molecules extracted from rat tail tendon (> 90% type I collagen) after tissue welding using an 808 nm diode laser and indocyanine green dye applied to the weld site. Mobility patterns on SDS-PAGE were identical in the lasered and untreated tendon extracts with urea or acetic acid. Pepsin incubation after acetic acid extraction revealed a reduction of collagen alpha and beta bands in lasered compared with untreated specimens. Circular dichroism studies of rat tail tendon showed absence of helical structure in collagen from lasered tendon. No evidence for covalent bonding was present in laser-treated tissues. Collagen molecules are denatured by the laser wavelength and parameters used in this study. No significant amount of helical structure is regenerated on cooling. We conclude that non-covalent interactions between denatured collagen molecules may be responsible for the creation of tissue welding.


Preliminary evaluation of a new high power diode laser. A high-powered semiconductor diode laser (805 nm) has recently been developed for medical use. The laser-tissue interactions of this wavelength have been compared with Nd:YAG (1064 nm). When used in the contact mode, the extent of tissue vaporization and zones of thermal necrosis produced by these two lasers were similar. The diode laser was also an effective and haemostatic laser scalpel. This compact laser unit has potential advantages over existing Nd:YAG lasers.


Optical properties of Intralipid: a phantom medium for light propagation studies. Intralipid is an intravenous nutrient consisting of an emulsion of phospholipid micelles and water. Because Intralipid is turbid and has no strong absorption bands in the visible region of the electromagnetic spectrum, and is readily available and relatively inexpensive, it is often used as a tissue simulating phantom medium in light dosimetry experiments. In order to assist investigators requiring a controllable medium that over a finite range of wavelengths is optically equivalent to tissue, we have compiled previously published values of the optical interaction coefficients of Intralipid, most of which were measured at a wavelength of 633 nm. We have extended the measurements of the absorption and reduced scattering coefficients from 460 to 690 nm and the total attenuation coefficient from 500 to 890 nm. These measurements show that, for stock 10% Intralipid, the absorption coefficient varies from 0.015 to 0.001 cm-1 between 460 and 690 nm, the reduced scattering coefficient varies from 92 to 50 cm-1 between 460 and 690 nm, the total attenuation coefficient varies from 575 to 150 cm-1 between 500 and 890 nm, and the average cosine of scatter varies from 0.87 to 0.82 between 460 and 690 nm. With these data, we discuss the design of an optically tissue-equivalent phantom consisting of Intralipid and black India ink.


Ultrafast imaging of tissue ablation by a XeCl excimer laser in saline. To determine the temporal evolution of laser induced tissue ablation, arterial wall specimens with either hard calcified or fatty plaques and normal tissue were irradiated in a 0.9% saline solution using a XeCl excimer laser (wavelength 308 nm, energy fluence 7 J/cm2, pulse width 30 ns) through a 600 microns fused silica fiber pointing perpendicular either at a 0.5 mm distance or in direct contact to the vascular surface. Radiation of a pulsed dye laser (wavelength 580 nm) was used to illuminate the tissue surface. The ablation process and the arising bubble above the tissue surface were recorded with a CCD camera attached to a computer based image-processing system. Spherical cavitation bubbles and small tissue particles emerging from the irradiated area have been recorded. The volume of this bubble increased faster for calcified plaques than for normal tissue.


Power density and exposure time of He-Ne laser irradiation are more important than total energy dose in photo-biomodulation of human fibroblasts in vitro. The absorption spectrum of human fibroblast monolayers showed several absorption peaks, among them one at a wave-length of 630 nm. Cultures of these fibroblasts were subjected to He-Ne laser (632.8 nm) irradiation of various energy doses by varying power density and exposure time. On three consecutive days the cell monolayers were irradiated for periods between 0.5 and 10 min. Laser power varied from 0.55 to 5.98 mW. Both cell number and collagen type I production were determined for each irradiation condition within one experiment. Results show that laser power below 2.91 mW could enhance cell proliferation (as determined by cell counting), whereas higher laser power (5.98 mW) had no effect. Stimulatory effects were most pronounced at irradiation times between 0.5 and 2 min. Collagen type I production (as determined by an ELISA) was affected in the opposite direction to cell proliferation: when the cell proliferation was increased, collagen type I production was decreased. From these experiments it is clear that exposure time and power density determine the effects of laser irradiation. Both stimulation and inhibition of the observed cell properties can be obtained with the same laser on the same cells.


Pulsed dye laser treatment of benign cutaneous pigmented lesions. Superficial benign cutaneous pigmented lesions that commonly present to the dermatologists and plastic surgeons have been treated by many conventional modalities such as dermabrasion, depigmenting creams as well as several types of lasers. Many of these treatment modalities lack specificity of injury, which has meant that normally pigmented and even non-pigment containing structures such as collagen as well as the hyperpigmented lesion itself have all been indiscriminately destroyed. This has resulted variously in hypopigmentation, hyperpigmentation, in addition to scar formation in some cases. A coaxial 504 nm laser with a pulse duration of 300 nsec was used to treat fifty two patients with superficial benign cutaneous pigmented lesions. Although the number of treatments required to clear the lesion varied according to the type of lesions being treated, on average, between 2 and 4 treatments were required to completely eradicate the superficial benign cutaneous pigmented lesions using 504 nm pulsed dye laser. The skin at the site successfully cleared of the pigmented lesion remained normal in skin color, texture, markings, and mobility.


EMLA for laser treatment of portwine stains in children. Vascular-specific lasers with pulse durations of between 300 and 500 microseconds are the treatment of choice for portwine stains (PWS), particularly in children. Although the discomfort felt following laser irradiation from a single pulse is transient, these sensations are intensified when multiple pulses are delivered over a confined area of skin. Because 75-80% of PWS are located in the head and neck regions, laser treatment of these sites tends to be more painful than those located in most other parts of the body. A prospective double blind randomized study, assessing pain during laser irradiation on PWS skin occluded with either EMLA, placebo, or no cream (control) was performed in 73 PWS subjects between 5 and 16 years of age. Analysis of the data showed that the pain scores for EMLA-treated sites were the smallest, the control scores tended to be the highest, with the placebo scores in the middle. The differences between the treatments were significant (P < 0.0001).


Treatment of lupus pernio with the flashlamp pulsed dye laser. Lupus pernio, a form of cutaneous sarcoidosis usually affecting the face, is often disfiguring and resistant to therapies, both medical and surgical. To our knowledge, there have been no previous reports of laser therapy for this condition. We describe a case of nasal lupus pernio successfully managed with the flashlamp pulsed dye laser.


[Antibiotic prevention and therapy of infectious complications in ERCP]. Endoscopic retrograde cholangiopancreatography (ERCP) may be complicated by bacteremia, cholangitis, or biliary sepsis. Bacteremia during ERCP implies a potential risk of endocarditis in patients with valvular prostheses or a previous history of infectious endocarditis. For these patients antibiotic prophylaxis prior to ERCP is recommended. Cholangitis or biliary sepsis may develop after ERCP in patients with obstructed bile ducts. In these patients antibiotics should be administered until adequate drainage of biliary obstructions is achieved. Antibiotic prophylaxis and antibiotic therapy must consider the spectrum of micro-organisms which is normally found in each of these situations. Regarding bacteremias associated with ERCP gram-positive cocci predominate, whereas cholangitis and biliary sepsis are caused mainly by gram-negative rods like Escherichia coli, Pseudomonas aeruginosa, or Klebsiella spp.


[Endoscopic sonography in esophageal cancer]. Esophageal carcinomas are visualized endosonographically as localized thickenings of the gullet wall with disruption of its echo-layers. The pT-stage is correctly assessed by endosonography in 84% (73-92%). In up to 20% overstaging in the early phases may be caused by accompanying inflammation. The sensitivity for diagnosing local lymph node metastases is 80% (69-90%). The method is well suited for monitoring the course during radio-chemotherapy and for detection of a relapse after operation. At the present time endosonography is the most efficient method in the locoregional staging of esophageal carcinomas. Especially in early tumor stages pT1 and pT2 it is clearly superior to computed tomography. In advanced stages (pT4) in up to 40% of cases marked tumor stenosis, that cannot be passed with the ultrasonic probe, prevents endosonographic staging. However, despite its excellent detail resolution the etiology of a circumscribed wall thickening cannot be determined with absolute accuracy by intraluminal sonography. Based on the echo-pattern inflammatory alterations and scar tissue cannot be definitely distinguished from malignant tumors.


[Acute liver failure in metastatic melanoma]. Only seven cases of occult malignancy clinically presenting as acute liver failure due to liver metastases have been outlined in literature so far. In six cases the primary tumor originated histomorphologically from pancreas, bronchus or mamma, in one case the patient died before histological diagnosis. This case report describes the only ten days lasting anamnesis of a 42-year-old man, who felt completely healthy before. Only the autopsy and the immunohistological staining of the taken biopsies led to the diagnosis of an amelanotic melanoma. The site of the primary lesion remained unclear.


Evaluation of four semi-synthetic Mycobacterium leprae antigens with sera from healthy populations in endemic and non-endemic areas. In order to determine the frequency of occurrence of antibodies to semisynthetic antigens of Mycobacterium leprae in clinically healthy nonpatient populations and to establish a 'baseline' for comparison with antibody frequencies in both patients with a history of leprosy and their contacts, ELISAs were conducted using representative sera from two areas: a leprosy endemic area, Cebu City, Philippines and a nonendemic area for leprosy Chicago, Illinois, USA. These sera were tested, by an indirect IgM ELISA, for the presence of antibodies reacting with four semisynthetic antigens based on the phenolic glycolipid I antigen of M. leprae: ND-O-BSA (natural disaccharide with octyl linkage to bovine serum albumin), NT-O-BSA (natural trisaccharide with octyl linkage to BSA), ND-P-BSA (natural disaccharide with phenolic ring linkage to BSA) and NT-P-BSA (natural trisaccharide with phenolic ring linkage to BSA). Using an OD reading > or = 0.16 as positive, the antigen with the lowest background seroreactivity was ND-O-BSA, which reacted with 5/398 (1.3%) sera from Cebu, and 3/426 (0.7%) sera from Chicago. A total of 10 (2.5%) of 398 sera from the endemic area reacted with at least one antigen and 5 (1.3%) sera reacted with all four semisynthetic antigens. Of the 426 sera from Chicago, 12 (2.8%) were reactive with at least one antigen and 3 (0.7%) were reactive with all four semisynthetic antigens. Mean ELISA values for the 22 positive sera for each antigen ranged from 0.17 to 0.3 OD units, while the mean values for all sera in each area ranged from 0.01 to 0.04 OD units for all four antigens. Reactivity of 14 of the positive sera to some antigens, but not all four semisynthetic antigens, indicated that the carrier and linker arms might be associated with this background reactivity. Investigation of alternative linker arms and carriers is warranted. We conclude that nonspecific background reactivity to the semisynthetic antigens representing the PG-I molecule of M. leprae is 0.7-1.3%, based on a > or = 0.16 OD cutoff value. From these data it was concluded that reactivity in individuals free of leprosy was low enough to warrant use of these antigens in a diagnostic setting, such as screening household contacts and highly endemic populations. When incidence and prevalence of leprosy are low, testing with these antigens would not be cost effective, unless applied to high risk individuals.(ABSTRACT TRUNCATED AT 400 WORDS)


Leprosy in French Polynesia. Epidemiological trends between 1946 and 1987. The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future.


Leprosy in French Polynesia. The possible impact of multidrug therapy on epidemiological trends. In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.


Leprosy control in 7 districts of south Sulawesi, Indonesia, 1986-91. This paper describes the leprosy control programme in 7 districts of the South Sulawesi Province in Indonesia. This province is reported to have the highest prevalence of leprosy in the country. The programme started in 1986 with re-registration of all patients on the cumulative registers. Strict criteria for admission of patients to MDT were initially applied. In 1990 it appeared that these criteria had been too strict, thus necessitating a second re-registration of patients still on DDS monotherapy. More flexible criteria for admission to MDT led to an increase in MDT coverage from 45% to 78% within 6 months. By April 1991, 5 years after the start of the programme, the registered prevalence had decreased from 4.4 per 1000 in 1986 to 1.6 per 1000; the coverage with MDT had increased from 6% in 1986 to 78%, and the case detection rate remained stable around 4 per 10,000 after an initial increase at the start of the programme.


Results of surgical procedures for the correction of foot-drop and of lagophthalmus due to leprosy. Leprosy mutilations of the muscles and skeleton can be relieved by reconstructive surgery, but evaluation of the results of these operations is seldom undertaken. Between 1975 and 1984, 59 leprosy patients were operated on at the Marie Adelaide Leprosy Centre, Karachi, Pakistan, for lagophthalmus with the transposition of the posterior tibial muscle. We were able to re-examine 39 patients: tibialis posterior transposition was performed 25 times, and temporalis transposition was carried out 33 times; 18 of the 25 patients with the tibialis posterior transposition were pleased with the result, 7 were not: 21 patients could extend their feet above the neutral position; 24 of the patients with the temporalis transposition were satisfied, 9 were not: complete closure was demonstrated in 21 eyes; Persistent corneal damage was noted in 15 eyes; 12 of the 23 male patients cared for themselves, 16 lived with their families; 7 of the 8 female patients lived with their families. The results of the rehabilitation, in relation to the degree of mutilation, are considered satisfactory for a developing country. These surgical procedures give a good result, provided they are followed by intensive physiotherapy.


Neuritic leprosy: epidemiology and therapeutic responsiveness. We studied epidemiology, progression and therapeutic responsiveness in 62 cases of neuritic leprosy. Numbness was the main presenting symptom. Mononeuritis involving the ulnar nerve, followed by the common peroneal nerve was the commonest presentation. The lepromin test was positive in 34 cases while a slit-skin smear was negative in all cases. We treated 20 of these cases with dapsone monotherapy and 5 cases (25%) developed a skin lesion after an average duration of 3 months' treatment. We treated 42 cases with a combination of dapsone and rifampicin, and 3 cases (7%) developed a skin lesion after an average duration of 2-6 months. The subsequent diagnosis in cases developing skin lesions was borderline--lepromatous in 1 case, borderline-tuberculoid in 4 cases, tuberculoid in 2 cases and indeterminate in 1 case.


Neurological examination of patients suffering from leprosy: is it worthwhile? We examined 28 male leprosy patients to discover if a more extensive neurological investigation than usual would be worthwhile in diagnosis and/or management. Our findings were fully compatible with what might be expected from a mononeuritis multiplex, either due to leprosy or other causes. The following observations are noteworthy. Changes of position sense and a decrease of some tendon reflexes were present in a minority of the patients. In soles of the feet, considered to be an- or hypaesthetic, some residual pain sensation could occasionally be detected. Functional testing of at least one muscle group (m. triceps surae) appeared to be more reliable than manual testing according to MRC criteria. We concluded that an extensive neurological examination is probably not required for diagnosis. It does provide, however, more accurate information on the extent of damage to the peripheral nervous system, which may be important for management and for assessment of treatment effects. The use of a myometer is advocated.


Primary neuritic leprosy in a black South African. A case of primary neuritic leprosy in a black South African is described, in which the multiple peripheral nerves were affected. The clinical picture and electrophysiological studies are in keeping with a picture of mononeuritis multiplex. Selective involvement of the facial nerve branches with normal blink reflex latencies was observed. The biopsy of the sural nerve disclosed features most consistent with borderline leprosy.


Estimated number of leprosy cases in the world. Planning for leprosy control requires estimates of the number of leprosy patients at different levels. During the period between the mid-1960s and the mid-1980s, global estimates had remained constant at between 10 and 12 million. The introduction of multidrug therapy (MDT) in many countries and the consequent reduction of the disease's prevalence has necessitated a reassessment of this. Based on available information and its interpretation, the number of leprosy cases in the world for 1991 has been estimated at 5.5 million. The number of individuals deformed by leprosy, including those cured of the disease, has been estimated at between 2 and 3 million.


Issues involved in the rapid assessment of the leprosy problem. Sample surveys for estimation can prove very expensive and time-consuming because of the enormous sample sizes usually required. Where sample surveys have to be undertaken, diagnoses should be limited to detecting a case of leprosy, without attempting skin smears etc. in order to classify by types. Usually enough knowledge is available on the approximate proportion of multibacillary (MB) cases in most communities, and this knowledge could be utilized for estimating the caseload by types of leprosy. Again intensive tracing of nonrespondents could be limited to either males or females depending on convenience, and well-known sex ratios among patients utilized for deriving estimates for the other sex. The type of rapid methods of estimation depend on three types of situations: (1) before multidrug therapy (MDT); (2) 5 years or more after MDT; and (3) less than 5 years after MDT. In the first situation one or more of the following methods are suggested: (i) extrapolation from registered cases; (ii) extrapolation from child prevalence; and (iii) conducting rapid village surveys. In situations where MDT has been introduced for 5 years or more the registered cases plus a small number, depending on local experience, would seem to be adequate. When MDT was introduced less than 5 years before, it is suggested that the prevalence rates be obtained by statistical interpolation drawing on the experience from areas which have had more than 5 years of MDT.


Defining a case of leprosy.

Defining a case of leprosy. The biological and technical hurdles confronting the development of new diagnostic tools are manifestly great in leprosy. Leprosy diagnosis in the field, for control as well as for research purposes, will have to remain, for the time being, predominantly clinical. It is important that the significance and relevance of diagnosing so-called 'early' lesions must be viewed in the context of the objectives of leprosy control. All evidence suggests that the majority of these 'cases' are not likely to progress in the individual, nor is there any evidence that these 'cases' are of any importance for the transmission of the disease. At its best, such 'cases' may be a sign of temporary infection which will disappear spontaneously within a few months without leaving any residual signs. It is more likely that the majority of these are not cases of leprosy. In making such a diagnosis its ethical implications on the individual, his family and the local society must be considered, given the intense social stigma this diagnosis will generate; besides the cost of treatment and the potential risk of serious side-effects due to treatment. It may be justifiable to have a broad definition if the incidence of leprosy is still high and all reported cases are to be accepted as valid. But once the backlog of cases has been detected and, as a result of control efforts, the number of new cases begins to decrease, there is a need to narrow the case definition for national statistics.(ABSTRACT TRUNCATED AT 250 WORDS)


Interleukin 6 modulation of second messenger systems in anterior pituitary cells. We investigated the effect of interleukin-6 (IL-6) on second messenger systems in anterior pituitary (AP) cells. The acute exposition of membranes derived from the pituitary gland to IL-6 did not modify basal and forskolin-stimulated adenylate cyclase (AC) activity, as well as inositol phosphate (IP) production and free [Ca(++)]i. Preincubation of AP cells with IL-6 for 20 min did not affect basal second messengers levels, while completely abolished the stimulation by VIP of AC activity, partially inhibited forskolin-stimulated cAMP formation and reduced TRH-stimulated IP production. Finally, the pretreatment of AP cells for 20 min with IL-6 also reduced the TRH-induced rise in free [Ca(++)]i.


Murine survival of lethal irradiation with the use of human umbilical cord blood. We have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over seventy percent (70%) of mice injected with HUCB survived 900 cGy or irradiation, which produced 100% deaths in the uninjected control animals. Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti-Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation.


Bioactivation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene by sulfation in the rat liver changes during the cell cycle. Sulfation activity towards N-hydroxy-2-acetylaminofluorene and 4-nitrophenol was determined in male rat liver cytosol at several time points after partial hepatectomy corresponding to G1-, S-, and M-phase. N-hydroxy-2-acetylaminofluorene sulfation activity decreased by 80% when hepatocytes entered the G1-phase. This lower activity was maintained during the S-phase and M-phase, but was restored when hepatocytes entered the G0-phase again. Sulfation activity towards 4-nitrophenol did not alter after hepatectomy. Various other cytosolic enzyme activities were determined after hepatectomy to investigate the specificity of the decrease in sulfation activity. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased in the S- and M-phase by maximally 80% and 60%, respectively. Glutathione-S-transferase and glutamate-pyruvate transaminase activity did not alter during the cell cycle. These results indicate that sulfation of N-hydroxy-2-acetylaminofluorene in hepatocytes may depend on the phase of the cell cycle. The relevance of the finding is discussed in relation to the resistance of proliferating (pre)neoplastic hepatocytes to the toxic and mitoinhibitory effects of N-hydroxy-2-acetylaminofluorene.


Hemodynamic effects of centrally administered, norcocaine in the rat. Norcocaine is the N-demethylated metabolite of cocaine. It is present in the CNS and is reported to be pharmacologically active. The present study was designed to evaluate the cardiovascular actions of norcocaine following central administration. Wistar Kyoto (WKY) rats were anesthetized with pentobarbital and instrumented for measurement of blood pressure and renal and hindlimb blood flow (via Doppler flowprobes). A cerebroventricular cannula was placed in the lateral ventricle for drug administration. Cocaine or norcocaine was administered centrally in a dose range of 0.025 to 4.0 mg/kg. Under the above experimental conditions, 4.0 mg/kg of norcocaine decreased blood pressure without a significant change in either hind limb or renal blood flow. Central administration of cocaine also produced a similar depressor response. In conscious, unrestrained rats, cocaine produced a pressor response while norcocaine did not significantly alter blood pressure. The depressor response to both cocaine and norcocaine in the anesthetized animal is speculated to be due to the local anesthetic properties of the drugs.


Ovarian atrial natriuretic peptide during the rat estrous cycle. The changes in ovarian levels of immunoreactive atrial natriuretic peptide (irANP) and arginine vasopressin (irAVP) were observed during the estrous cycle of rat. We also demonstrated the synthesis of ovarian ANP. In adult 4-day cycling rats, ovarian level of irANP was found to be the highest on proestrus and was to be the lowest on diestrus. Ovarian irANP level inversely correlated with ovarian level of irAVP. On reverse-phase HPLC, two distinct peaks of ovarian irANP, high and low molecular weight forms, existed in the each stage of the estrous cycle. However, no significant changes in plasma and atrial concentrations of ANP were observed during the cycle. The rat ovary contained mRNA coding for ANP. These data showing the synchronized cyclic change of ovarian irANP and irAVP with the estrous cycle suggest that the ovary locally synthesizes ANP and ovarian ANP may play regulatory roles on the follicular fluid dynamics.


The effect of dexamethasone on neuropeptide Y concentrations in specific hypothalamic regions. Neuropeptide Y (NPY) is a major hypothalamic peptide which is implicated in the regulation of energy balance and in the activation of the hypothalamo-pituitary adrenal axis. This study aimed primarily to determine the effects on regional hypothalamic NPY levels, of catabolism and weight loss induced in rats by the synthetic glucocorticoid, dexamethasone, injected daily at a dose of 0.4 mg/kg for 7 days. NPY concentrations were significantly raised in the paraventricular nucleus (PVN) of male Wistar rats (45%, p = 0.009; n = 10) compared with saline-injected controls (n = 10). Body weight (p less than 0.001) and food intake (p less than 0.001) were significantly reduced, plasma insulin concentrations were increased (p less than 0.001), but there was no change in glucose concentrations. Chronic dexamethasone treatment did not cause the marked NPY increases in the arcuate nucleus (ARC) and other hypothalamic regions which have been observed in other catabolic states causing weight loss. One possible explanation is the high insulin levels induced by dexamethasone, which may have prevented compensatory hyperphagia by suppressing an increase in hypothalamic NPYergic activity. We also examined the acute effects of a single dexamethasone injection on regional hypothalamic levels, to determine whether the drug had a direct action separate from that due to sustained weight loss. In the acute study, groups of rats (n = 7) were examined at 4 h after a single injection of dexamethasone or saline. NPY concentrations were significantly increased in the lateral hypothalamic area (LHA), (60%, p = 0.008) when compared with saline-injected controls, but there was no change in body weight or glucose or insulin concentrations during the 4h interval. Altered transport or release of NPY in the lateral hypothalamic area may be a result of acute feedback regulation by glucocorticoids on the hypothalamus.


Ventricular defibrillating properties of catecholamine uptake inhibitors. Ventricular fibrillation (VF) is a fatal event in humans unless electrical defibrillation is applied within minutes. Recent publications describe spontaneous termination of VF in various animals and even in humans. Certain drugs can transfer a fatal, sustained VF (SVF) into a self-terminating, transient VF (TVF). Based on results obtained in animals of various species and ages, we have suggested that the occurrence of TVF requires a high cardiac catecholamine level at the time of VF. According to our hypothesis, drugs which decrease catecholamine reuptake by the sympathetic nerve terminals will increase the ability of the heart ventricles to defibrillate spontaneously. In the present study, we examined the effects of desipramine, maprotiline, mianserin, iprindole, cocaine and amphetamine on the type of VF in cats exhibiting SVF prior to the treatment. The results show that the ability of these compounds to transfer SVF to TVF is closely related to their potency to inhibit catecholamine reuptake. The establishment of the catecholamine related mechanisms of TVF may lead to the development of a new class of antiarrhythmic-defibrillatory drugs.


Alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori--a possible mechanism behind gastric injury. Two standard Helicobacter pylori strains showed significant cytosolic alcohol dehydrogenase activity and produced considerable amounts of acetaldehyde when incubated with an ethanol containing solution in vitro. The alcohol dehydrogenase activity of the Helicobacter pylori strains was almost as high as that found in Klebsiella pneumoniae and far greater than that in Escherichia coli or Campylobacter jejuni. The amount of acetaldehyde produced by cytosol prepared from Helicobacter pylori exceeded that by any of the other bacteria studied. The bacterial production of acetaldehyde--a highly toxic and reactive substance--could be an important factor in the pathogenesis of Helicobacter pylori associated gastric injury and increased risk of gastric cancer.


Regulation of arginase production by glucocorticoid in three human gastric cancer cell lines. Gastric cancer tissues have high levels of glucocorticoid receptors (GR) and arginase. To investigate the interrelation of glucocorticoid, GR and arginase, three human gastric cancer cell lines (AZ-521, NUGC-3, KATO-III) were treated with hydrocortisone in the presence or absence of a glucocorticoid antagonist RU38486. GR were found to be present in all three lines, and hydrocortisone significantly increased the production of total arginase in all 3 lines. The induction of arginase production by hydrocortisone was inhibited by RU38486. These findings suggest that the regulation of arginase production by hydrocortisone in gastric cancer cells is mediated through GR.


Validation of the antral mucosal/submucosal sleeve preparation: studies of gastrin and acetylcholine release in response to luminal stimulation. In the present study we developed an experimental model for direct assessment of antral endocrine cell and cholinergic neural responses to luminal stimulation. A sleeve of antral mucosal/submucosal tissue was prepared from rat antrum, mounted in perfusion chamber, and perfused in both luminal and submucosal compartments. Morphological and functional integrity of the antral sleeve were confirmed by histological examination and measurement of protein synthesis. Antral gastrin release was assessed in response to luminal stimulation with acid, peptone and distension. Luminal acid (pH3) inhibited basal gastrin release by -70.4% and luminal peptone stimulated gastrin release to 210% above control (p < 0.02). Distention of the antral sleeve by hydrostatic pressure (3-25cm H2O) caused stepwise and significant increase in gastrin release that was reversible. 3H-acetylcholine was stimulated significantly by KCl (56mM) to values twice control. In summary, these results establish the integrity and responsiveness of the antral sleeve to pharmacological and luminal stimulation. The antral sleeve may be a useful model in assessing antral function in response to luminal stimulation.


Similarities between the akinesia induced by carbachol microinjections into the pontine reticular formation and neuroleptic catalepsy. We reported previously that microinjections of carbachol directly into the pontine reticular formation of rats induced intense akinesia. In the present article we report results of tests for rigidity, righting, bracing and clinging which were conducted with the purpose to characterize behaviorally this type of akinesia. After injections of 5-15 micrograms/0.5 microliter of carbachol into the pontine reticular formation the rats were cataleptic, were not rigid when equilibrium was not challenged, had strong righting reflexes and strong bracing and clinging responses. This type of akinesia is different from the catatonia induced by systemic morphine (20 mg/kg IP), but similar to the catalepsy induced by systemic injections of haloperidol (5 mg/kg IP). It is thus suggested that the cataleptic state produced by topical carbachol in the pons is related to the dopaminergic mechanisms important for the cataleptic effect of the neuroleptic drugs.


Nephrectomy and a newly identified binding site for angiotensin II in the rat adrenal cortex. Angiotensin II (Ang II) binding sites in adrenal glands of nephrectomized rats were investigated by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as ligands. Ang II binding site was increased to 161% in the cortex and decreased to 67% in the medulla 48 h after nephrectomy. In the medulla, the AT2 antagonist (PD123177, 5 microM) inhibited specific binding by 90% whereas the AT1 antagonist (DuP753, 5 microM) inhibited by only 10%. In contrast, in the cortex, neither DuP753 (5 microM) nor PD123177 (5 microM) substantially inhibited the binding. Binding in the presence of either the AT1 or AT2 antagonist was abolished by the simultaneous presence of both antagonists. These results suggest the presence of a new Ang II binding site with unique pharmacological properties and differing from currently known subtypes of Ang II receptors, in the adrenal cortex after nephrectomy.


Both cyclooxygenase and lipoxygenase inhibitor partially restore the anorexia by interleukin-1 beta. Since the peripheral prostaglandin synthetizing system may at least partly involved in the anorexia that follows central interleukin-1 beta (IL-1) administration, this study was undertaken to investigate the effect of ibuprofen (ip), selective cyclooxygenase blocker and AA 861, selective lipoxygenase inhibitor, on changes of food and water intake by a single injection of IL-1 (2 micrograms/rat, ip). We demonstrated that food and water intake were suppressed by peripheral administration of IL-1. Throughout the entire observation periods, suppressed food intake was partially restored to control levels by ibuprofen, while water intake completely restored. In addition, no significant differences about water/food intake were observed in the IL-1 + ibuprofen-treated groups, respectively. In the next experiment, IL-1 induced anorexia was also partially restored to the control level following pretreatment with AA 861. These results may suggest that other mechanism including lipoxygenase blocker besides prostaglandin production may be involved in IL-1 induced anorexia.


The ANF-C receptor is not linked to adenylyl cyclase inhibition in bovine pulmonary artery endothelial cells. The possible inhibition of adenylyl cyclase activity by atrial peptides selective for the ANF-C receptor was investigated in bovine pulmonary artery endothelial cells. In these cells isoprenaline, guanine nucleotide and forskolin dose-dependently increased activity over basal levels. In the presence of rANF(99-126), these dose-dependent increases were not reduced, nor were they affected by the ANF-C receptor selective analogue C-ANF(102-121). Furthermore, the selective analogues rANF(103-123) and des[Cys105,Cys121]rANF104-126 had no effect on basal or stimulated adenylyl cyclase activity. It can be concluded that ANF-C receptors are not linked to inhibition of adenylyl cyclase in these cells.


Changes in vitamin A status following prolonged immobilization (simulated weightlessness). A study was conducted to investigate the effects of a simulated weightlessness induced by chronic immobilization on vitamin A status. To simulate the stress condition of weightlessness, rats were suspended for 10 days in a special jacket to which metal chains were attached. Animals received a commercial stock diet. Control rats were pair-fed in reference to the suspended rats. As compared with the control, prolonged immobilization resulted in a decrease in body weight gain and an increase in adrenal weight occurred. In the suspended rats, serum concentrations of retinol and retinol-binding protein (RBP) declined. Hepatic retinyl palmitate content increased, and the hepatic retinol level was decreased. The prolonged immobilization led to significantly reduced retinyl palmitate levels in the testis and lung as well as lowered testicular retinol levels. The results suggest that the stress state induced by prolonged immobilization caused accumulation of hepatic retinyl palmitate, decreasing the serum retinol concentration and retinyl ester content in the extrahepatic tissues.


The effect of short-term lipid infusion on liver function and biliary secretion in rats. This study was undertaken to determine the effect of various lipid emulsions on the hepato-biliary system in rats. Rats were randomly divided into six groups and infused continuously for 48 hr with either long-chain triglycerides (LCT), medium-chain triglycerides (MCT) or a mixture of MCT and LCT. One group infused with physiological saline solution served as controls. Throughout this period the rats received a fat free diet ad libitum. During the last hour of lipid infusion bile was collected for determination of bile flow and composition. Subsequently, the rats were sacrificed and the morphology and lipid content of the liver determined. Only LCT lipid emulsions induced morphological changes and increased liver cholesterol content. In two rats infused with radiolabeled LCT, no labeled cholesterol was found in the liver, indicating that the excess hepatic cholesterol level may originate from enhanced cholesterol mobilization to the liver. Biliary cholesterol and phospholipid concentrations in LCT-treated rats were also elevated, as was the lithogenic index, whereas the other emulsions had no such effects. None of the emulsions affected the plasma liver function tests or bile flow. We therefore conclude that the lithogenicity of the bile in rats is directly related to the lipid components of the total parenteral nutrition and the type of triglyceride infused.


Effect of dietary fish oil on the rate of very low density lipoprotein triacylglycerol formation and on the metabolism of chylomicrons. The mechanism by which omega 3 fatty acids lower plasma triacylglycerol levels was investigated. Rats were fed fish oil, olive oil (10% fat by weight) or a nonpurified diet (4% fat by weight) for 15 days. Lipoprotein lipase was inhibited by intra-arterial administration of Triton WR 1339 to estimate hepatic triacylglycerol output. Rats fed the olive oil diet showed a higher rate of triacylglycerol formation than rats fed the omega 3 fatty acid diet or the low-fat diet. All three groups showed identical rates of removal from plasma of intraarterially administered artificial chylomicrons that had simultaneously been labeled with cholesteryl [1-14C]oleate and [9,10(n)-3H]triolein. Liver radioactivity and total fat content were lowest in rats fed the fish oil diet, indicating that omega 3 fatty acids were preferentially metabolized in liver. Chylomicrons obtained from donor rats fed either fish oil containing [14C]cholesterol or olive oil containing [3H]cholesterol were removed at similar rates when infused together intraarterially into recipient animals. A slower formation of plasma very low density lipoprotein triacylglycerols in rats fed fish oil is probably due to a faster rate of oxidation of the fatty acid chains in the liver resulting in decreased plasma triacylglycerol concentrations.


Effect of dietary fats on some membrane-bound enzyme activities, membrane lipid composition and fatty acid profiles of rat heart sarcolemma. The effect of various dietary fats on membrane lipid composition, fatty acid profiles and membrane-bound enzyme activities of rat cardiac sarcolemma was assessed. Four groups of male weanling Charles Foster Young rats were fed diets containing 20% of groundnut, coconut, safflower or mustard oil for 16 weeks. Cardiac sarcolemma was prepared from each group and the activities of Na+, K(+)-ATPase, 5'-nucleotidase, Ca(2+)-ATPase and acetylcholinesterase were examined. ATPase activities were similar in all groups except the one fed coconut oil, which had the highest activities. Acetylcholinesterase activity was also similar in all the groups, however, it was significantly higher in the group fed mustard oil. No significant changes were observed among the groups in 5'-nucleotidase activity, in the cholesterol-to-phospholipid molar ratio and in sialic acid content. The coconut, safflower and mustard oil diets significantly increased cholesterol and phospholipid contents and the lipid-to-protein ratio of cardiac sarcolemma as compared to feeding the groundnut oil diet. The fatty acid composition of membrane lipids was quite different among the various groups, reflecting the type of dietary fat given. The total unsaturated-to-saturated fatty acid ratio was not different among the various groups; however, the levels of some major fatty acids such as palmitic (16:0), oleic (18:1) and linoleic (18:2) acids were significantly different. Cardiac sarcolemma of the group fed safflower oil had the highest polyunsaturated fatty acid content. The results suggest that dietary fats induce changes not only in the fatty acid composition of the component lipids but also in the activities of sarcolemmal enzymes involved in the regulation of cardiac function.


Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases. We investigated the effect of maternal alcohol consumption on cell number, gangliosides and ganglioside catabolizing enzymes in the central nervous system (CNS) of the offspring. Virgin female rats of the Charles Foster strain were given 15% (v/v) ethanol in drinking water one month prior to conception and during gestation and lactation. At 21 days postnatal age, the offspring were sacrificed and the brains were separated into cerebrum, cerebellum and brain stem to investigate possible regional variations. Compared to controls, wet weight of cerebrum, cerebellum and brain stem, and of spinal cord was decreased in the pups exposed to alcohol. DNA and protein contents were also found to be lowered in all the CNS regions of the pups exposed to alcohol. Conversely, maternal alcohol consumption was found to increase the concentration and the content of total ganglioside N-acetyl-neuraminic (NANA) in CNS of the pups. In addition, alcohol treatment was found to induce alterations in the proportions of individual ganglioside fractions. Interestingly, these alterations are somewhat different than those observed in the neonatal brain and spinal cord of the pups subjected to prenatal alcohol exposure. The alterations in the proportions of ganglioside fractions were shown to be region-specific. Maternal alcohol consumption resulted in decreased activities of sialidase, beta-galactosidase, beta-glucosidase and beta-hexosaminidase. The results suggest that the alcohol-associated increases in ganglioside concentration may be at least partly due to the decreased activities of ganglioside catabolizing enzymes.


Fluorospectroscopic analysis of the fluorescent substances in peroxidized microsomes of rat liver. The fluorescent substances formed in rat liver microsomes in the course of lipid peroxidation were investigated by fluorescence techniques. The fluorescence emitted from peroxidizing microsomes continuously increased as lipid peroxidation progressed, while the steady-state fluorescence anisotropy increased and then reached a plateau. A similar increase was observed in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in peroxidizing microsomes. The fluorescence from peroxidized microsomes consisted of at least three species having short, middle or long fluorescence lifetimes. The lifetimes and relative amplitudes of fluorescence were unaffected by the extent of lipid peroxidation. Both fluorescence of the chromolipids extracted and the proteins isolated from peroxidized microsomes had the same characteristics in fluorescence lifetimes as the fluorescence from whole peroxidized microsomes. Thus, these lipids and proteins appear to be the major biological substances responsible for the fluorescence emanating from whole peroxidized microsomes. Furthermore, fluorescent substances formed in microsomes seem to increase in quantity rather than change in quality as lipid peroxidation progresses.


A study of the composition of fish liver and body oil triglycerides. Silver-ion high-performance liquid chromatography (Ag(+)-HPLC) was used to study the range and variations in molecular species of triglycerides from industrial, retail and laboratory extracted fish oils. These were contrasted with a typical plant oil. Selected fish oils were fractionated and the fatty acid distribution of the fractions determined by gas-liquid chromatography. Fish oils gave a characteristic Ag(+)-HPLC profile, typified by sharp, intense peaks at the start of the chromatogram and broad, multiple nongaussian peaks for the late eluting components. Triglycerides ranging from those that were wholly saturated to those containing 16 double bonds were isolated. Cod (Gadus spp.), saithe (Pollachius virens) and monkfish (Squatina squatina) liver oils gave similar triglyceride profiles. Mackerel (Scomber scombrus), capelin (Mallotus villosus) and herring (Clupea harengus) body oils gave characteristic triglyceride profiles which were associated with high concentrations of 20:1 and 22:1 fatty acids. Only small amounts of these particular triglycerides were observed for menhaden (Brevoortia spp.), South African anchovy (Engraulis capensis) and Indian sardine (Sardinella longiceps) oils, all of which contained minor amounts of these acids. The latter oils contained highly unsaturated triglycerides, whereas only traces of these were noted for the former. Chromatography with Ag(+)-HPLC can be used for the rapid screening of fish oils and for selecting those oils rich in polyunsaturated acids that may be suitable for enrichment. Cottonseed oil gave well-defined and discrete peaks. Similar peaks were observed in the chromatogram of Omega-combination, a mixture of primrose and fish oils. Thus, fish, plant and a mixture of these oils can be readily distinguished.


Lipid composition and mitochondrial respiration in warm- and cold-adapted sea bass. The response to cold of liver and heart membrane lipid composition and mitochondrial respiration in reared sea bass (Dicentrarchus labrax L.) was investigated. Fish acclimation was followed during the natural seasonal cycle from August to March. The data on the fatty acid composition of liver and heart polar lipids and on total lipids of liver mitochondria and microsomes did not indicate any increase in unsaturation in response to cold. The enzyme complexes of the liver and heart mitochondrial respiratory chain showed a repeated negative compensation for cold acclimation. The constancy of the break in the Arrhenius plot of liver cytochrome oxidase (EC 1.9.3.1) was consistent with the lack of homeoviscous adaptation of membrane lipids. A thermoadaptive strategy based on the reduction of sea bass metabolic activity is suggested.


Improved resolution of 31P nuclear magnetic resonance spectra of phospholipids from brain. A method is described wherein the resolution of 31P nuclear magnetic resonance spectra of the lipophilic fraction from a Bligh-Dyer extract of rat brain can be enhanced. The lipids are dispersed as micelles in aqueous solution with sodium deoxycholate, and spectral resolution is further optimized by adjusting the pH and by removing ions from the solution. The application of the method to the study of aging in rat brain serves as an example.


One-step synthesis of radioactive acyl-CoA and acylcarnitines using rat liver mitochondrial outer membrane as enzyme source. Rat liver mitochondrial outer membrane enriched preparations have proven to be a convenient enzyme source for synthesizing coenzyme A (CoA) and carnitine esters of radioactive fatty acids. These membranes are simple to isolate and they retain acyl-CoA ligase and carnitine palmitoyltransferase activities well upon storage. Enzyme purification is not required. A novel aspect of the present procedure is that the same enzymatic incubation step allows both the acyl-CoA and the acylcarnitine esters to be obtained simultaneously when carnitine is present, but produces acyl-CoA ester only when carnitine is not included. Under the conditions described, the conversion of [1-14C]octanoic acid to the respective esters was about 95%; the corresponding figure for [1-14C]palmitic acids was over 70%. The procedure seems suitable for synthesizing the labeled CoA and carnitine esters from a variety of radioactive fatty acids.


The origin of palmitic acid in brain of the developing rat. A rat milk substitute containing lower amounts of palmitic and oleic acid in the triacylglycerols in comparison to natural rat milk was fed to artificially reared rat pups from day 7 after birth to day 14. Pups reared by their mother served as controls. Free trideuterated (D3) palmitic acid [(C2H3)(CH2)14COOH, 98 atom % D] and free perdeuterated (D31) palmitic acid [C15(2)H31COOH, 99 atom % D] in equal quantity were mixed into the triacylglycerols of the milk substitute in an amount equal to 100% of the palmitic acid in the triacylglycerols. A control milk substitute contained unlabeled free palmitic acid in an amount equal to 100% of the palmitic acid in the triacylglycerols of the milk substitute. The objective was to determine if palmitic acid in the diet contributed significantly to the palmitic acid content of developing brain and other organs. The methyl esters of the fatty acids were analyzed by gas chromatography and the palmitic acid methyl ester was examined by fast atom bombardment mass spectrometry. The proportion of deuterated methyl palmitate as a percentage of total palmitate was determined; 32% of the palmitic acid in liver and 12% of the palmitic acid in lung were trideuterated and perdeuterated palmitic acid in approximately equal amounts. The brain, by contrast, did not contain the deuterated palmitic acid moiety. Quantitation of palmitic acid and total fatty acids revealed a significant accumulation in organs in the interval from 7 to 14 days of age. Under our experimental conditions, labeled palmitic acid does not enter the brain. Consequently, we conclude that the developing brain produces all required palmitic acid by de novo synthesis.