Epithelial proliferation in response to gastrointestinal inflammation.

Intestinal inflammation seems invariably to be associated with increased epithelial proliferation. In the small bowel the pathological consequences of this area an increase in the crypt proliferative compartment and a decrease in the absorptive villus compartment, which can lead to malabsorption. In the colon, it is more difficult to examine changes in cell proliferation, but using Ki67, epithelial proliferation has been shown to be increased in ulcerative colitis and parasitic infection. The teleological advantage of increasing epithelial proliferation during intestinal inflammation is presumably in an effort to get rid of parasitized or infected epithelial cells, or to rapidly replace cells which have been lost. Rejection of helminth parasites from rodent small bowel is associated with partial villous atrophy and crypt hypertrophy, which is probably part of the host response making the mucosa inhospitable to the parasites. The short-term nutritional disadvantage of malabsorption is outweighed by the long-term advantage of being parasite-free. However, when the intestinal inflammation is elicited by a dietary constituent, the consequences are only pathological. At the moment there is no information as to the mechanisms by which inflammatory cells alter mucosal morphology and epithelial renewal. The restructuring of mucosal morphology in the flat-mucosa involves considerable adaptation of the connective tissue elements of the lamina propria. Whether this occurs in response to changes in epithelial renewal is not known. Finally, it is clear that activated T cells in the lamina propria can produce a flat-mucosa. In diseases such as Trichuris dysentery and ulcerative colitis there is no or very little T cell activation, even though epithelial proliferation is increased. Increased epithelial proliferation therefore may occur in response to different inflammatory stimuli.


Epithelial secretory response to inflammation.

As suggested by this and previous reviews, the neuroimmunoregulation of intestinal secretion is a complex series of endocrine, neurocrine, paracrine and autocrine interactions between the underlying cells in the mucosa and submucosa and the intestinal enterocyte. Under normal conditions, the balance of each of these systems is delicately controlled, thus allowing for normal, consistent intestinal function. However, when this finely-tuned system is altered, such as in a diseased state, the resultant effect is an amplification of the host defense response. Initially thought to be protective against further insult, this local immune response, if allowed to continue uncontrollably, can exacerbate the disease process.


Excitatory and neurotoxic actions of platelet-activating factor on rat myenteric neurons in cell culture.

At micromolar concentrations, PAF causes intense excitation and elevation of intracellular Ca in a subset of myenteric neurons. When applied for more than about 10 seconds, these concentrations of PAF kill a subset of myenteric neurons. The excitation and elevation of Ca levels are accompanied by increased membrane conductance and enhanced synaptic activity. The effects of brief applications are reversible, but responses to subsequent applications of PAF are substantially reduced. If such responses can be elicited in enteric neurons by the concentrations of PAF that are generated in vivo, they would account for the potent ability of PAF to evoke neurally-mediated secretory responses in GI tissues.


Antigen-mediated effects on epithelial function.

In summary, immediate hypersensitivity reactions to luminal antigens occur in the intestine and result in pathophysiology including increased permeability and ion secretion. The mechanism involves activation of mast cells with neural amplification (FIG. 5). Released mediators/neurotransmitters may act independently or synergistically on the epithelium to elicit Cl ion secretion. In addition, a cyclooxygenase product of arachidonic acid metabolism, possibly of mesenchymal cell origin, may be a common mediator. However, additional effector cell(s) besides mast cells are undoubtedly involved. This system demonstrates undeniably the concept of neuro-immuno-physiology of gut mucosa.


Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1.

IL-1 beta is one of the most potent centrally acting inhibitors of gastric acid secretion in rats. Sites of action have been located in the anterior/preoptic area and paraventricular nucleus of the hypothalamus where other biological activities of IL-1 have also been described. IL-1 beta action is, so far, quite unique to this cytokine and its action is not reproduced by IL-2 or TNF alpha. The IL-1 effect involves prostaglandin pathways and is unrelated to CRF. Similarly, systemic injection of IL-1 induces a long lasting inhibition of acid secretion through prostaglandin-dependent mechanisms. Several findings support the possibility that the effect of systemic IL-1 can be CNS-mediated and/or exerted at the periphery through local release of PG in the stomach. Exogenous IL-1 given into either the circulation or the cerebrospinal fluid also inhibits gastric injury induced by a variety of experimental models (stress, aspirin, ethanol). Such a protective effect is mediated through the inhibition of acid secretion and prostaglandin release, although other mechanisms may also contribute. Whether endogenously released IL-1 beta exerts a protective role in the gastric mucosa is still to be investigated.


Intestinal physiology in the parasitized host: integration, disintegration, and reconstruction of systems.

As noted in the introduction, the major objective in discussing gut inflammation in the parasitized host is to underscore the difficulty in establishing whether an inflammation-induced change represents a physiological adaptation or maladaptation (Fig. 3). Deciding whether a specific physiological adjustment, even one that contributes to disease, serves a useful function depends on the perspective of the observer who is in possession of information to make a critical judgment. This is like considering adaptations from an evolutionary sense where the significance of a change that evolved as a consequence of natural selection must be interpreted relative to the long-term "goal directedness" of that change, e.g., relative to its contribution to reproductive fitness. Because of the contributions of inflammation to both symptoms of disease and to the development of functional immunity, the parasitized host provides a means whereby both negative and positive effects of mucosal responses can be studied simultaneously. A careful analysis of the consequences of inflammation is important in contemplating the meaning of "neuroimmunophysiology of gastrointestinal mucosa."


Immunopathology of NSAID-gastropathy: inhibitory effects of interleukin-I and cyclosporin A.

The present study demonstrates that CSA is capable of inhibiting indomethacin-induced leukocyte adherence to the vascular endothelium, and can reduce the severity of indomethacin-induced gastric mucosal injury. These results are therefore consistent with the hypothesis that leukocyte (particularly neutrophil) adherence is a critical event in the pathogenesis of NSAID-induced gastropathy. The mechanism through which CSA inhibits leukocyte adherence is not clear, and warrants further investigation. This study also confirmed the protective effects of IL-1 in experimental NSAID-gastropathy, and demonstrates that one of the ways the IL-1 may protect the mucosa is through its ability to inhibit the release of proinflammatory mediators (e.g., PAF) and promote the release of antiinflammatory mediators (e.g., nitric oxide). IL-1 modulated the release of these mediators from peritoneal mast cells at doses in the pg/ml to ng/ml range. IL-1 can inhibit the ability of neutrophils to respond to chemotactic stimuli and can prevent LTB4-induced neutropenia. Inhibition of neutrophil function by IL-1 may therefore account for its ability to reduce NSAID-induced gastric mucosal injury. Whether or not effects of IL-1 on the production of mediators such as nitric oxide and PAF is an underlying mechanism for the inhibitory effects on neutrophil function remains to be determined.


Nerve remodelling during intestinal inflammation.

The intestinal mucosa contains a dense nerve network and many inflammatory cells, and these may interact through the exchange of regulatory molecules. Evidence suggests that intestinal mucosal mast cells are innervated, and it is known that the density of this cell type changes significantly in nematode-infected rats. Recent data indicates that rat jejunal mucosal nerves remodel after Nippostrongylus brasiliensis infection, with degenerative and regenerative phases during the acute and recovery stages of inflammation. Seven weeks postinfection there is a net increase in the density and number per villus of mucosal nerves. These changes suggest that mucosal nerves exhibit structural plasticity in inflamed tissues, which must impact on interactions between the enteric nervous system and other mucosal elements in disease.


The movement of solutes and cells across tight junctions.

The TJ is a highly dynamic rate-limiting barrier for passive transepithelial solute flow. It is not only physiologically regulated but is modulated in various disease states as well. Such modulations occur as a result of epithelial cell interactions with immune cells or immune cell products and thus epithelial barrier function appears to be regulated in disease states.


[Cochlear implants in children].

The development of surgically implantable hearing aids that are placed directly in the cochlea where they send electrical impulses to the cochlear nerve is a major break-through for patients whose hearing loss is so severe as to make conventional electroacoustic hearing aids ineffectual. Initially used only in adults, this method has gradually been extended to pediatric patients. To benefit from a cochlear implant, the patient must fulfill a number of criteria which are specified in this article. Following preoperative investigations, the decision is taken during a meeting of all the care providers involved, i.e., the surgeon, ENT phoniatrist or audiophonologist, hearing aid specialist, special education provider, speech therapist, psychologist, and other members of the health care staff. Team work is thus essential both before and after the procedure. The implant selected can be intracochlear or extracochlear and single-channel (one electrode) or multi-channel (several electrodes). Each team selects the implantation technique and type of implant they use according to their preferences and specific criteria. The authors use a multi-channel intracochlear system except in the rare instances where complete ossification of the cochlea requires use of an intracochlear mono-channel system. They have inserted implants in 29 patients to date. The cochlear implant has unquestionably had a significant impact of the life of these patients.


[Nasal polyposis in children. Diagnostic and therapeutic problems].

Nasal polyposis in an infrequent condition in children and may occur as part of a variety of diseases. Treatment is difficult and often yields disappointing results. The purpose of this paper is to review the diagnostic problems raised by nasal polyposis and to analyze current surgical approaches. Twenty-seven patients with a mean age of 12 years, including 12 with nasal polyposis as part of another disease state (cystic fibrosis in 10 and Woakes disease in 2) and 15 with idiopathic nasal polyposis, underwent endonasal ethmoidectomy. The decision to perform this procedure was based on severity of initial clinical symptoms, lack of improvement under medical treatment, and availability for close postoperative follow-up. Twenty-six patients were followed-up for a mean period of three years ad a half. Complete recurrence occurred in 15% of patients and partial recurrence in 8%. In all the other cases, the ethmoidal cavity was satisfactory and nasal symptoms resolved completely. Etiopathogenic aspects of nasal polyposis are reviewed, as well as the therapeutic approach according to whether or not the disease occurs as part of another syndrome.


[Choanal atresia: management and surgical treatment. Study of 50 cases].

Diagnosis of choanal atresia should lead to multidisciplinary investigations to look for other malformations which may or may not be part of the CHARGE syndrome. These concomitant defects have an adverse effect on prognosis in patients with choanal atresia. They seem to be more common in patients with bilateral choanal atresia due to a bony septum. Local investigations include nasal fiberoptic endoscopy to obtain a direct view of the atresia and a CT scan study to determine the type of obstruction. In neonates, treatment rests on transnasal perforation of the septum followed by stenting for four to six weeks. However recurrence is common and requires subsequent use of another therapeutic procedure. In patients with failed transnasal perforation or unilateral choanal atresia discovered at a later age, surgery through the palatal route seems to be virtually radical and can be carried out from eight months of age. Recently developed CO2 laser therapy is, in the opinion in of the authors, an elegant and simple means for transnasal treatment of fibrotic restenosis which, in many cases, obviates the need for transpalatal surgery.


[Bacterial epidemiology of acute otitis media].

Since the middle of the 1980's, Haemophilus influenzae is the most common bacterial species responsible for acute otitis media in France, followed by Streptococcus pneumoniae. Haemophilus influenzae has maintained its leading position since 1985, but the rate of pneumococcal acute otitis media is increasing fairly steadily. The other recent change with regard to the distribution of bacterial agents is the emergence, four years later than in North America, of Branhamella catarrhalis which currently accounts for 10% of cases of acute otitis media. Modifications in the behavior of microorganisms in relation to antimicrobials usually given to treat upper respiratory tract infections have occurred. Staphylococcus aureus and Branhamella catarrhalis have always exhibited marked resistance to ampicillin due to the production of beta-lactamases. Resistance of Haemophilus influenzae to ampicillin has been increasing gradually since 1985, again with a lag of a few years as compared with the United States; at present, this form of resistance is seen in approximately 35% of strains. More recently in France, 20% of pneumococcal strains recovered from middle ear pus have been shown to have abnormal susceptibility to penicillin. These changes in the behavior of the two main pathogens, i.e., Haemophilus influenzae and Streptococcus pneumoniae, require implementation of rigorous multiregional epidemiologic surveillance programs and may justify reappraisal of current therapeutic approaches.


[Current therapeutic approach to cervicofacial lymphangiomas in children].

Twenty-four cases of cervicofacial lymphangioma treated between 1984 and 1991 are reported. The therapeutic approach is discussed. Because the therapeutic problem depends on whether or not the airways are involved, an endoscopic evaluation and a CT scan study should be included in the workup. In the five patients with limited lymphangiomas, complete surgical exeresis was feasible and yielded good results. Sclerosing injections are an alternative to surgery in this situation. In patients with pharyngeal or laryngeal infiltration or involvement of the mediastinum, the prognosis is extremely grim and surgery is still the mainstay of therapy despite the potential for recurrence due to the fact that only incomplete exeresis can be performed. Tracheostomy was required in two patients.


[Management of caustic burns of the esophagus in children].

The authors describe their therapeutic approach to caustic burns of the esophagus in pediatric patients. Initially, early endoscopic evaluation is carried out under general anesthesia using a stiff tube then a fiberoptic endoscope. During this procedure, severity of esophageal damage is determined: stage I: mild burn requiring no treatment; stages II and III: severe burn with a risk of subsequent esophageal stricture requiring insertion of a nasogastric stent. A repeat endoscopy is performed after approximately 25 days to evaluate healing. If healing has occurred, the nasogastric tube is removed and dynamic esophagography is performed 2 to 7 days later. Patients with strictures should be treated with repeated endoscopic dilatation at gradually increasing intervals. Surgery is indicated only in patients with complications or multiple strictures after failure of dilatation; trans-mediastinal colon esophagoplasty with removal of the burned esophagus is the method of choice.


[Deafness screening in children by otoacoustic emissions. Current data].

Hearing impairment should be detected in early childhood. Among available screening techniques, acoustic oto-emission testing is a rapid, reliable, noninvasive method which specifically investigates peripheral hearing but does not provide data on auditory nerve centers. This functional test should be carried out within a few days of birth in infants with risk factors for hearing impairment.


[Severe aplasia of the ear: management and surgical indications].

Severe aplasia of the ear raises both a cosmetic and a functional problem. Surgery is often performed starting at four or five years of age but early management is essential. The need for a hearing aid should be evaluated at the age of six months. At birth, the infant should have investigations for concomitant malformations, which are common, and for etiologic factors. Functional surgery to create a canal, tympanic membrane, and chain of ossicles should be performed only in bilateral forms. Satisfactory cosmetic results can be achieved by cartilage autografting according to Brent's technique.


[Current therapeutic indications in laryngeal stenoses in children].

Among pediatric patients with laryngeal stenosis, acquired forms are now more common than congenital forms. External surgery is not always warranted except in complete or tight obstructions. After establishing the diagnosis by endoscopy, consequences on respiration and phonation should be assessed before deciding on the most appropriate treatment: abstention, medical therapy, endoscopic treatment, or surgical treatment by the cervical route. Surgical laryngoplasty techniques have changed radically over the last twenty years. The Cotton procedure is the most widely used. Another available method is the cricoid-split technique. These laryngoplasty procedures can be performed from birth and tracheostomy is now warranted only after failure of initial surgery.


[Syndrome of obstructive sleep apnea in children].

Sleep apnea syndrome (SAS) in children has been identified only recently. Its incidence is unknown but seems to be rising. The cause is usually an obstruction (enlarged tonsils) that alters the fragile physiologic mechanisms responsible for maintaining the upper airways open when the child is sleeping. Diagnosis of SAS rests on clinical findings. The parents should be questioned as to the frequency over time of the various symptoms, of which most occur during the night: snoring, difficult breathing, respiratory pauses. Sleep polygraphy studies are indicated only in specific situations. The main cause is enlargement of the adenoids and tonsils. Cardiovascular complications may develop; weight gain and statural growth, psychomotor development and development of the face may be altered. Chronic snoring without apneas should be considered as a form of SAS. Treatment rests mainly on surgery (removal of the adenoids and tonsils).


[Vertigo in children].

The main difference between childhood and adulthood vertigo is that the evaluation of symptoms and examination pose special challenges in pediatric patients, depending on age. Vertigo in pre-teenage children is similar to vertigo in adults. In contrast, although benign paroxysmal vertigo, vestibular neuronitis, and Ménière's vertigo occur in children, the distribution of these conditions is different from that seen in adults. After vestibular and cochlear investigations as well as a CT scan or MRI study to outrule a tumor of the posterior cerebral fossa, the diagnosis of vestibular vertigo is established. Often, the diagnosis proposed cannot be considered as final and requires reappraisal according to the long-term course. Collation of case-reports with highly accurate documents is essential in order to strive to develop more satisfactory approaches.


[Why and how should serous otitis media be treated?].

Serous otitis media is an extremely commonplace condition in pediatric patients and tends to resolve spontaneously. Only some forms warrant treatment. Indications for treatment include frequent superinfections, lasting hearing impairment with adverse consequences on socialization, or debilitation of the tympanic membrane carrying a risk for the ear. Tympanostomy tubes are a palliative treatment for serous otitis which restores hearing within a few hours and eliminates unfixated retractions of the tympanic membrane within a few weeks. Tympanostomy tubes may lead to complications including otorrhea and perforation of the tympanic membrane and should therefore be used only in patients with severe otitis media. Etiologic treatment of serous otitis rests on restoration of satisfactory nasal ventilation (education to improve nose-blowing, adenoidectomy), improvement of eustachian tube patency (corticosteroids), and modification of the characteristics of middle ear secretions (mucolytic agents and mucomodifying agents).


[Cancer of the stomach: for a revised strategy].

The "revisionist" approach to therapy of gastric cancer needs a previous demonstration of the qualitative comparability of Japanese and western treatments of gastric adenocarcinoma. Early gastric cancer is far more common in Japanese than in Occidentals, but its character is the same, and for identical stages and treatments, the prognosis is the same. But many western studies show serious methodological deficiencies (staging, anatomopathological examination...), as well as a serious lack of interest in adjuvant therapy, a potential source of progress. We propose a 4-point therapeutic approach inspired by the Japanese example: a greater methodological rigor, standardization of lymphadenectomies, the definition of therapeutic subgroups to receive optimal treatments, the development of new adjuvant treatments.


[Value of a "floppy" Nissen in the treatment of gastroesophageal reflux. Apropos of 117 cases].

The Nissen fundoplication is the most widely used antireflux procedure. However this operation is associated with several specific complications. To prevent these complications, an alternative antireflux procedure ("floppy" Nissen) has been designed. This investigation was conducted to investigate the effects of the floppy Nissen performed on 117 patients, between 1978 and 1990. Indication for surgery was the endoscopic discovery of stage I and II oesophagitis (59 cases), III and IV oesophagitis (25 cases) or an associated disease (gallstones: 25 cases, duodenal ulcer: 8 cases), pH monitoring used preoperatively in 47 cases showed an important reflux in 33 cases (70%). Preoperative manometry exploration (71 cases) showed a low pressure of the low oesophageal sphincter (LOS) in 63 cases (89%). The "floppy" Nissen procedure was performed over a length 4 to 6 cm. The folds of the diaphragm were closed back behind the oesophagus in 40 cases. During the postoperative period the pH-data were restored to normal range in 73% (18/26 cases), and the value of the LOS was restored in 74% (19/26 cases). The mean duration of clinical follow-up study of 99 patients was 3.22 years. Improvement in clinical symptoms was noted for 86%; 13% had specific Nissen complications (9 gall-bloat syndrome, 4 intermittent dysphagia). Six patients had to be reoperated. This technique allowed good control of the reflux symptoms, with a low incidence of mechanical complications.


[Prognostic incidence of blood transfusion in 753 patients operated for colorectal adenocarcinoma].

Do transfusions have a deleterious effect on the survival after surgery for colorectal carcinoma (CRC)? Among 1,221 patients operated on for a CRC between 1969 and 1988, 753 patients having undergone a curative surgical procedure with a follow-up of at least six months were evaluated retrospectively. 134 patients (17.2%) did not receive any transfusion; the others 619 (82.80%) received transfusions including 150 with packed red blood cells only. Transfused and non transfused patients were compared. Among the classical indicators for disease free survival, the only valuable parameter was the pathological classification, but it was not discriminant between transfused and non transfused patients. Prognostic value of transfusions were evaluated with regard of the components and the quantity of transfused items, the time of transfusions (either per- or perioperative), the surgical procedures and the tumor location on colon and rectum. The 5 years survival of transfused patients was less than for non transfused patients (56.3% versus 61.7%, p > 0.05 NS), but only the transfusions of more than 5 packed red blood cells worsened significantly the prognostic. (5 years chi 2 = 5.7; p < 0.02). Adjustments with pathologic analysis and time evolutive indications for transfusions did not alter those results. These results point the fact that transfusions could influence survival after surgery for CRC and stress us to limit reasonably transfusions.


[Minimal intestinal preparation before colectomy for cancer. Experience of 189 cases].

189 cases of colectomy for cancer have undergone limited bowel preparation by one or two enemas the day before surgery. The anastomosis has been performed manually with a continuous suture of resorbable material. Hospital mortality is 1.6% for the whole series and limited to 0.5% for elective resections despite the old age of the patients included (70.6 +/- 11 years, with 40.7% more than 75 years). Morbidity rate is 13.9% and of 2.6% for local septic complications. No clinical anastomotic dehiscence was demonstrated. From these results, poor local bowel preparation does not appear to be a risk factor of colectomy for cancer.


[Postoperative morbidity and mortality of infectious complications of colonic diverticulosis: multifactorial study].

The objective of this study was to determine parameters influencing the mortality due to postoperative adverse events, by taking into account surgical techniques and many other perioperative parameters. From 1967 to 1989, 83 patients were operated for pericolic abscess (level 1, n = 22), pelvic abscess (level 2, n = 38) purulent peritonitis (level 3, n = 16) and fecal peritonitis (level 4, n = 7). Surgical techniques were: first colostomy with drainage (n = 21), first resection without immediate anastomosis (n = 34), and first resection with immediate anastomosis (n = 28). The overall complications were 51% (n = 42) with a mortality of 28% (n = 23). During univariate analysis, variables linked to postoperative complications were neurologic events (p < 0.0001), cirrhosis (p = 0.01), current treatment by steroids (p = 0.007), infectious level (p = 0.002), first colostomy (p = 0.005) and first resection with anastomosis (p = 0.007). Postoperative mortality was linked with neurologic events (p < 0.0001), age (p = 0.005), infectious level (p = 0.04), first colostomy (p = 0.005), and first resection with anastomosis (p = 0.0012). Logistic regression determined 3 independent variables influencing complications: neurologic events (p < 0.0001), first colostomy (p = 0.01), and infectious level (p = 0.002). The mortality determined by multivariate analysis was dependent on 3 variables: neurologic events (p < 0.0001) first colostomy (p = 0.007) and age (p = 0.01). The adjusted relative risk was 17 for neurologic events and 6 for first colostomy.


[Validation of the measurement of hepatic volume by three-dimensional computed tomography].

The aim of this work was to verify experimentally the reliability of 3D CT scan in measuring hepatic volumes. Eight livers were dissected from corpses. The referring liver volume was determined by measure of its hydric shift. The correlation coefficient R was 0.93 (p < 0.001) on 5 mm/5 mm 3D sections, 0.92 (p < 0.001) on 10 mm/10 mm 3D sections and 0.94 (p < 0.0006) on 5 mm/10 mm 3D sections. The paired t-test also showed a 5% risk correlation between the two measurements. Although in vivo imaging is slightly different from in vitro, 3D CT scan seems to be a reliable method to determine an hepatic volume without increased X-ray irradiation.


[Acute hepatic artery thrombosis in pediatric liver transplantation: surgical thrombectomy and in situ fibrinolysis].

In pediatric liver transplantation, hepatic artery thrombosis usually leads to graft loss, early due to hepatic necrosis when it occurs during the first week following the transplant procedure, or later due to biliary complications. Liver retransplantation is the usual attitude. However, urgent surgical hepatic arterial thrombectomy to restore the blood flow can be successful when early diagnosis is made with Doppler ultrasound examination and angiography. Four hepatic arterial thrombectomies were performed as an emergency with additional intra-hepatic arterial fibrinolytic treatment, in three children, 1.5, 3 and 5.5 years of age. Mean duration between the first signs of hepatic artery thrombosis and thrombectomy was 16 hours. None of the children had an urgent liver retransplantation. A complete success was obtained in one case, with normal liver function tests and patent hepatic artery on the Doppler ultrasound examination at the present time. In the two other cases, hepatic artery thrombosis recurred, in spite of repeated thrombectomy in one case; following this attempt complications of hepatic artery thrombosis occurred in the two patients: ischemic necrosis of the left lobe (1 case), biliary leak (1 case) and stenosis of the common bile duct (2 cases). A complete success in one case and a partial success in the two others lead us to advocate urgent thrombectomy and in situ fibrinolytic treatment when early diagnosis of hepatic artery thrombosis is made.


[Cholecystectomy by celioscopy: indications and safety of the method. Apropos of a consecutive series of 300 patients].

We performed a laparoscopic cholecystectomy in 300 patients with gallstone disease complicated or not. The rate success was 97%, however involved the pathology might be. Indeed, 15% of the patients had an acute cholecystitis (10% catarrhalis, 5% empyema). Twenty-four patients with common bile duct stones had a complete endoscopic management of the biliary disease: endoscopic sphincterotomy and laparoscopic cholecystectomy. Operative mortality was absent and overall morbidity was 3.7%, exclusively minor.


[Role of resection of the celiac plexus in the analgesic treatment of pancreatic cancers].

The aim of this study was to evaluate the pain relief related to resection of the celiac plexus in pancreatic carcinoma. This technique was attempted in 26 consecutive patients and performed in 23 (feasibility: 88%), whose mean age was 64 years. Before surgery, patients were divided into two groups: patients not treated by narcotic analgesics (group 1, n = 10) and patients treated by narcotic analgesics (group II, n = 13). Surgery was indicated in 22 patients for pancreatic resection or by-pass, and in 1 patient for pain relief after an unsuccessful per-cutaneous celiac plexus block. Resection of the celiac plexus was always performed via a trans-peritoneal approach, after mobilization of the head of the pancreas and the duodenum. Only the right half of the celiac plexus was resected in 4 patients (17%) due to technical difficulties. Pathologic examination was performed in 16 patients (8 patients from each group) and neoplastic involvement was observed only in 3 patients of group II. There was no operative death. Two complications related to this method occurred (9%). One patient developed a chylous ascites and was treated conservatively. In a second patient, an occlusion of the celiac trunk was complicated by infarction of the spleen and of the left lobe of the liver; this patient was reoperated and his subsequent post-operative course was uneventful. In group I, eight patients (80%) did not require narcotic analgesics after resection of the celiac plexus. Two failures occurred, one immediately after surgery and one delayed. In group II, seven patients (53%) did not require narcotic analgesics; 6 of these 7 patients died. Six failures occurred, 4 early after surgery and 2 delayed. Three of the 4 early failures occurred in patients who underwent resection of the right half of the celiac plexus. The authors concluded that resection of the celiac plexus seems to be an effective pain treatment in pancreatic carcinoma. However, resection must be bilateral to provide analgesia. Specific morbidity of this technique may lead to the use of non-surgical methods if surgery is not indicated for pancreatic resection or by-pass.


[Left pancreatectomy with preservation of the spleen without its pedicle. Apropos of 13 cases].

Overwhelming post splenectomy infections in childhood were first described by King and Shumaker in 1952. This septic risk, although a matter of controversy, also exists in adults. Thus, splenic conservation must become a surgical concern in left pancreas resections for benign or traumatic diseases. The authors report their experience with a simplified procedure in which the splenic pedicle is resected "en bloc" with the left pancreas. This technique has been employed in thirteen patients, in whom spleen could be preserved in twelve, without operative mortality and a low morbidity rate.


[Pancreas divisum, chronic pancreatitis and diabetes mellitus. Improvement by pancreaticojejunostomy].

The relationship between pancreas divisum and chronic pancreatitis is controversial. We report the cases of two patients aged 40 and 53 years suffering from recurrent pancreatitis and known to have histologically proven idiopathic chronic pancreatitis. One patient had insulin dependent diabetes. Pancreatography demonstrated in these two cases a pancreas divisum with a dilated dorsal pancreatic duct. A pancreatico-jejunostomy was performed, associated in one case with splenopancreatectomy for pseudo-cyst. With a follow-up of 32 and 78 months, both patients were free of symptoms and the diabetic patient had normal blood glucose levels with diet alone. The clinical history of the patients suggests a relationship between pancreas divisum and chronic pancreatitis and that pancreatico-jejunostomy may improve pancreatic pain and pancreatic function.


[A direct approach and a crease-resistant prosthesis: two simplifications of subperitoneal hernioplasty].

With experience of six already known techniques, the authors have developed a personal procedure combining three main principles: 1) large and direct exposure of the preperitoneal space, 2) the mesh, supple but not soft, needing no fixation, 3) outline of this mesh adapted to the concave shape of the pelvic wall, and avoiding the risk of a ventral hernia. The original points of this technique are the following: approach along the lateral border of the rectus muscle through its sheath, the initial exposure of the iliopsoas muscle and retropubic space, and the cutting of the mesh extending far beyond the borders of the inguinal and femoral orifices, with a flap reinforcing the posterior aspect of the rectus muscle. One hundred and two consecutive patients (173 hernias, 48 recurrences) were operated upon, and all but two were followed for a mean period of 36.8 months. Morbidity was low, with no prosthesis infection, and there was no recurrence or incisional hernia. The authors emphasize the simplicity and the rapidity of this technique, without advocating it as a routine operation, since it carries, like all prosthetic techniques, the potential for sepsis and preperitoneal fibrosis.


[Cystadenocarcinoma with peritoneal involvement (pseudomyxoma peritonei). Is surgical resection alone sufficient?].

We present our experience of 10 cases of pseudomyxoma peritonei treated in our regional hospital between 1978 and 1992. We note the rarity of this disease; the catastrophic macroscopic appearance may mislead the in experienced surgeon. Preoperative diagnosis is usually easy when confronted with a mass in an ascitic abdomen, with the help of ultrasonography and CT-scan, and above all after abdominal puncture which produces pathognomonic gelatinous fluid. Most cases are derived from the ovary and appendix. Treatment is surgical and aggressive; we adopt the protocol proposed by Sugarbaker which combines repeated surgery and local and systemic chemotherapy. The relatively good survival, even in the malignant cases, seems to be improved by this treatment.


[Late revascularization of the renal artery: what are the prognostic criteria?].

Two patients with non functioning silent kidney on excretory urography and renal artery occlusion on angiography, underwent renal artery revascularization without severe hypertension or renal failure. Angiographic appearance of collateral circulation, histologic evidence of intact viable glomeruli and a normal sized kidney are necessary for successful results. Renal blood flow was restored in the two patients but one had slight return of function and the other patient showed no evidence of improvement. Both patients presented criteria for revascularization. The first case was a minor success on the renal scintigraphy. The return of renal function did not occur in the second case because of preexisting renal pathology. We therefore recommend histologic examination before every renal artery revascularization for chronic occlusion.


[Primary hyperparathyroidism in children].

Primary hyperparathyroidism in children is an extremely rare condition. Slightly more than a hundred cases have been published in children or adolescents aged under 16. Forms with a neonatal presentation, the most rare, should be viewed apart since they rapidly become life-threatening. They involve hyperplasia of the chief cells of the parathyroid glands. Treatment is always surgical and should be rapid, consisting of total parathyroidectomy with autotransplantation. Primary hyperparathyroidism in older children more closely resembles that seen in adults. Sporadic forms are most often due to an adenoma and familial forms, which may occur alone or within the context of a polyendocrine syndrome, are most often due to hyperplasia. Treatment consists of parathyroidectomy, the extent of which depends upon the familial context, visual investigative findings and results of frozen section histology at the time of exploratory cervicotomy. Regardless of the age of the child, family investigation is always required to detect primary hyperparathyroidism occurring in the context of a hereditary disorder.


[Early weight-bearing after osteosynthesis by THS hip screw in cervico-trochanteric fractures].

A second generation hip screw was designed in the laboratory to allow unlimited immediate weight-bearing in elderly patients with cervico-trochanteric fractures. The use of this device in 300 operated patients demonstrated that it provided the same capacity for weight-bearing as total hip prostheses, but with a lower morbidity and better and longer lasting functional results. Thus, in patients with a mean age of 77 years, one half of whom suffered from an unstable fracture: the operation was minimally traumatic (reduction on an orthopaedic table, no surgical access to the fracture site, operating time less than one hour); complications were consequently rare (no deep sepsis, no dislocation) in contrast with 5 to 10% of deep sepsis or dislocation with prostheses; early unlimited weight-bearing was permitted by the 5th day in every case and was achieved by the 10th day in more than 80% of cases (30% of whom were able to walk unassisted with crutches); an essential point, the design of the material prevented dismantling on weight-bearing and preserved the morphology of the hip (telescoping of the fracture site never exceeded 20 mm, mean:11 mm). Consolidation was obtained in every case by 6 to 8 weeks. The mortality at 3 months was identical to that observed with prostheses (18%, related to physiological age). The length of hospital stay and the duration of rehabilitation were considerably shortened, as 37% of patients returned to their previous residence by the 45th postoperative day. This resulted in a marked saving in medical costs for each patient (as patients previously returned home after an average of 145 days).(ABSTRACT TRUNCATED AT 250 WORDS)


Results of surgical treatment of patients with Crohn's disease.

A follow-up study of 98 patients suffering from Crohn's disease was performed to evaluate the recurrence rate of the disease and the patients' ability to cope socially with this chronic disease. Eight patients were decreased and one had emigrated, thus 89 of the patients were contacted. Two of the patients had died of Crohn's disease and another two had died of adenocarcinoma of the large bowel involved in Crohn's disease. 83% of the patients had been operated on. The cumulative rate for recurrences resulting in reoperation using the life table method was 34% at 10 years and 55% at 20 years. Even after an enterostomy, the patients who had only large bowel involvement had the best quality of life and were most able to work. On the other hand, due to the higher recurrence rate, operated patients with both small and large bowel involvement found it most difficult to cope with the disease.


Characteristics of jaundice and cholestasis in a Finnish population.

A prospective study of a Finnish population of about 250,000 patients with jaundice or unjaundiced cholestasis was carried out. During a two-and-a-half year period altogether 343 patients entered the study. The male/female ratio was 46%/54%. The mean age was 64.9 years (range 19-92). Extrahepatic obstructive diseases constituted two-thirds of the cases both in the jaundiced and unjaundiced cholestatic patient groups. The leading extrahepatic diseases causing jaundice were gallstone disease (61%) and pancreatic carcinoma (19%). Among the nonobstructive intrahepatic diseases causing jaundice, the most frequent diseases were alcoholic liver disease (32%) and viral hepatitis (21%). In patients with unjaundiced cholestasis, the spectrum of diseases resembled that of the jaundiced patients, gallstone disease and pancreatic carcinoma being the largest disease groups. In conclusion, extrahepatic obstructive processes seem to be the major aetiology of jaundice and unjaundiced cholestasis in our study population.


When is routine operative cholangiography necessary? An evaluation of 200 consecutive patients operated on for gallbladder stones.

Operative cholangiography (OC) was performed during open standard cholecystectomy in 195 of 200 consecutive patients. The cholangiography was considered suspicious for choledochal stones in 28 patients (14%). Both choledochotomy and choledochoscopy were carried out. Stones in the biliary tree were found in 17 patients and in 11 cases choledochotomy was negative. Cholecystectomy was performed on an emergency basis in 46 patients, 15 of them underwent choledochotomy and in 11 (24%) bile duct stones were found. In 154 electively operated patients six (4%) had choledochal stones. Based on preoperative history choledochal stones were suspected in 30 electively operated patients but only eight had stones in the biliary tree at the time of operation. The percentage of false positive cholangiograms was 6% in the whole material, and unsuspected choledochal stones were diagnosed in 5% respectively. It is recommended that operative cholangiography should be performed routinely in patients subjected to emergency cholecystectomy. In elective operations selective use is acceptable.


Results of 500 general surgery patients operated on in the ambulatory surgery unit.

This study examined the outcome of 597 general surgery operations performed on 500 patients in the ambulatory surgery unit of the University Hospital of Kuopio between November 1989 and May 1990. Endoscopies were excluded from the study. Spinal (41.0%) and local infiltration (31.2%) were the most often used forms of anaesthesia. During anaesthesia 15.8% of patients required treatment for hypotension, and 13.6% for bradycardia. Of the 351 (70.2%) patients, who returned the one month follow-up questionnaire, 41 (11.7%) had visited a doctor postoperatively. The main reasons for this visit were pain in 41 (100%), minor bleeding in 24 (58.5%) and inflammation in 16 (39.0%) patients. No deaths or other major complications were observed. 92% of the patients were satisfied with the treatment and anaesthesia.


Recurrences after inguinal herniotomy in children. Long time follow-up.

Three hundred consecutive children all under 18 years of age were treated for inguinal hernia by herniotomy by the same surgeon from 1970-1985. Hernioplasty was not performed. Seven patients had a recurrent hernia, i.e., a cumulative recurrence rate of three per cent after a median follow-up of 12 years (range 5-19). Five of seven (71%) recurred within five years after the operation, while only two recurred from the 5th to the 15th year. Long term follow-up is necessary to assess incidence of recurrence after inguinal herniotomy in children.


Bronchoscopic laser photodestruction of benign tumours in the trachea and large bronchi.

Potentialities and results of laser bronchoscopic surgery of exophytic benign tumours of the trachea and bronchi are described. The material includes 37 patients (33 men and 4 women) aged 28-69 (mean age 51 years). Tumours were removed by the Nd-YAG laser. In six patients laser photodestruction was combined with electrosurgery. In 31 patients manipulations were done via bronchofiberscope under local anaesthesia and in six patients via a rigid bronchoscope under general anaesthesia. Complete removal of pathologic tissues was achieved in all patients. During 1-5 years of follow-up none of the patients developed recurrent tumours.


Hip fractures in urban population in Finland.

We studied prospectively the occurrence of hip fractures among the over 49-year-old urban populations (n = 88,206) in the cities Tampere, Jyväskylä and Kotka in 1989 and compared the results with a parallel Scandinavian multicentre study. During 1989, there were 266 inhabitants who were treated for a hip fracture, 213 of them were women. Women had in 132 cases a femoral neck fracture and in 81 cases a trochanteric fracture, and the corresponding numbers for men were 22 and 31. Among women, the total hip fracture incidence in Jyväskylä (n = 22) was the lowest when compared with the ones in Tampere (n = 47) and Kotka (n = 36). These incidences were on average lower than in the other Scandinavian cities studied in parallel. The all over ratio of femoral neck/trochanteric fractures was 1.1 in Tampere, 3.0 in Jyväskylä and 2.2 in Kotka and in Tampere, women had 9.3 times more femoral neck fractures than men. Our study showed that in Finland in three major cities the hip fracture incidence was lower than what has been similarly registered in corresponding urban populations in other Scandinavian countries. We also point out that the relative part of trochanteric fractures appears to be increasing.


Platelet activation during acute phase after multiple trauma.

The acute phase after multiple trauma is associated with both thrombotic phenomena and a bleeding diathesis. To evaluate the activation of platelets, beta-thromboglobulin (BTG) in plasma and serum and thromboxane B2 (TxB2) in serum were measured in 14 patients with multiple trauma. BTG in plasma was significantly increased on days 1, 2 and 10 to 14 after the trauma. The highest median value 90 micrograms/l was measured on day 1. BTG in serum was significantly reduced 1 to 7 days after the trauma (median levels 4450-9100 micrograms/l). TxB2 was significantly reduced (median levels 18-97 ng/l) on days 1 to 14. The increased plasma levels of BTG is due to the posttraumatic activation of platelets in vivo. The reduced levels of serum BTG and TxB2 reflect the deficient functional capacity of circulating platelets to respond to extreme stress. Therefore, platelet count alone may correlate poorly with the haemostatic potential and may underestimate the need of platelet transfusions.


Primary malignant schwannoma of the small bowel.

Primary malignant schwannoma of the small intestine is an extremely rare disease. We report a primary malignant intestinal schwannoma of the small bowel in a 66-year-old woman, who was admitted to the hospital because of fatigue and anaemia. On clinical examination there was a solid mass at the abdomen. Ultrasound scanning showed an abdominal tumour. Computed tomography showed a mass in the area of the pancreatic tail involving the small intestine. At laparotomy a 10 x 10 cm tumour was found in the proximal jejunum, and 50 cm of the small intestine was resected. The histology of the lesion corresponded to a malignant intestinal schwannoma. The results of previous studies and of our report suggest that the diagnosis of malignant intestinal schwannoma may be difficult, and to exclude malignant conditions laparotomy and surgical excision of the tumour are adequate in the management of this type of lesion.


[Periprosthetic membrane island flap with axial pedicle. Experimental study on the effect of time and expanded volume].

This experimental study, conducted in the rat, assessed the influence the volume of expansion and time after expansion on the vascularised area of a periprosthetic membrane axial pedicle (epigastric) expanded island flap. 15 Wistar rats were operated on and divided into 3 series according to the expanded volume (20 cc, 40 cc) and the time (1, 2 months). The membrane vascularisation derived from the pedicle was study by microradiography based on geometric parameters. At equal times, the volume essentially increased the length of the pedicle and had little effect on the vascularised area. For equal expanded volumes, increasing latency time increased the length and especially the width of opacification derived from the pedicle. The periprosthetic membrane axial pedicle island flap is an experimental entity whose vascularised area, obtained after a certain amount of expansion, is influenced more by time than by the volume of expansion.


[Refinement of partial and total reconstruction of the nose].

In this surgical field, sophisticated refinements of the complex structures of the tip, the alae and the columella are required to achieve a corrected rather than a reconstructed appearance of the nose. The conventional corrective rhinoplasty should complete the reconstructive work. Apart from skin grafts and composite grafts for small repairs, the author currently uses only the fronto-parieto-occipital flap (Galvao) for total reconstruction, and the fronto-temporal flap (Schmid-Meyer), as well as the complex frontal island flap with the supratrochlear artery as pedicle for partial repairs. The author has abandoned several other techniques. The principle of the two last techniques consists in the preformation of the apico-columello-alar structure with the appropriate skin and cartilage grafts already in the donor area. For the correction of secondary stenoses, the author occassionally uses composite grafts from the interior aspect of the auricular crus helicis.


[Repair techniques in perforations of the nasal septum].

According to my experience extending over more than 20 years (more than 100 cases) in the treatment of septal perforations, I have the deep conviction that all techniques using local flaps should actually be considered to be obsolete, as the blood supply is insufficient. Perforations with diameter up to 4 cm can be closed in a one stage procedure with extensive dissection of the muco-perichondrium and mucoperiosteum of the septum, the vault and the vestibular and cavity floor. The hole in the quadrangular plate can be reduced by a push back or push down manoeuver of part of the cartilage. For closure of perforations larger than 4 cm in diameter, I use a 2-3 stage procedure using a composite buccal flap with three layers (mucosa-cartilage and mucosa) and a gingivo-labial pedicle. Thus all kinds and sizes of perforations can be closed surgically avoiding the use of silicone obturators which only enlarge the hole.


[Value of interrupted resection of the lateral crus in surgery of the nasal tip].

Three goals have to be achieved in the surgery of the tip of the nose. Separately or joined together, they contribute to modify the height, rotation or width of the tip. Interrupting resection of the upper legs gives the ability to modify both the projection and the rotation of the tip. The authors present this technique, emphasizing the precise location of the knee of the upper legs and the interest to perform interrupting resections laterally to this region.


[Esthetic pinching of the globular nasal tip. Technical note].

A conservative technique designed to simple reduce the width of nasal tip is presented. It consists of approximation of the anterosuperior segments of alar lateral crus after their elevation on median pedicles. A marginal inferior band of alar cartilage is left adherent to the nasal mucosa. The procedure is completed without cartilaginous excision. We tried this technique in ten rhinoplasties and the results were satisfactory. The nasal tip narrowing obtained has no significant effect on either tip projection and position or nostril shape.


[Treatment of cleft lip and palate: long-term results].

Since 1958, 900 children with cleft lip and palate were operated on at the University Hospital Brugmann in Brussels. Until 1981, the children were operated at 6 months for the lip and at 18 months for the palate with two flap palatoplasties. Since 1982, R. Malek's technique and sequence were adopted. The results after 5 years follow-up are analyzed between two groups of 50 and 49 children operated with the two techniques. Growth of the maxillary arch and phonation are well improved in the second group, but no improvement was observed in terms of hearing.


[Partial anterior chondrotomy in the correction of prominent ears. Apropos of 140 re-examined cases].

336 patients have been operated for protruding ears. 140 of them have a long term postoperative follow-up. The anterior partial chondrotomies are opposed to the other surgical procedures and give the opportunity for a comparative and retrospective study. Surgical indications and procedures, use of antibiotics, postoperative follow-up, and complications are studied. 95% of results are good or very good whatever the surgical procedure. The authors remain the posterior and anterior access for partial chondrotomy.


[Evaluation of the Mustardé technique in the treatment of prominent ears. Apropos of 1100 patients].

The analysis of a homogenous series of 1,100 patients with prominent ears confirmed the reliability of the Mustardé technique and the reversibility of the iatrogenic deformities related to this procedure.


[Cutaneous retraction. Data from liposuction and other clinical procedures].

The remarkable capacity of the skin to stretch is used in the skin expander technique. In parallel, the skin is also able to retract, which is very useful for the plastic surgeon. This ability to retract may open the road for new techniques. Suction lipectomy, which allows removal of large volumes of fat without skin resection, is a privileged technique for the study of retractability characteristics. This study compares the pre and postoperative conditions in 392 cases of body liposuction and 108 cases of cervicofacial liposuctions, to determine the factors which influence skin retraction. It appears that age and the total amount of fat removed have an incidence on the time needed to obtain the final result. However the treatment site emerges as a determinant factor on the potential of the skin to retract postoperatively. In practice, the skin elasticity appears to be very different in different treatment sites, and considerable variations can even be observed between two neighbouring regions. In the neck and cheeks the skin seems considerably more retractable than in other sites, and we can trace the boundaries of the optimal retractability for the liposuction: "the golden triangle at the neck". The considerable plasticity of the skin overlying the neck contrasts with the poor ability of facial skin to retract. On the body, the skin resumes its previous form in the vast majority of patients (90%). These data, derived from a liposuction study, may be compared with other clinical observations.(ABSTRACT TRUNCATED AT 250 WORDS)


[Keloid cicatrix of the face and neck. Apropos of 81 cases treated in Dakar].

The authors report their experience of the treatment of 81 cases of keloid scars in Africa. Many methods have been proposed and used but they do not consistently lead to good results. The fact that many operations have been indicates their back of efficacy. The natural tendency towards recurrence dictates the correct choice of operation. The best result is obtained by combining surgery with radiotherapy.


["Pseudo-kite" flap of the index finger with LLL-plasty in the reconstruction of the first commissure].

The authors describe a peninsular diamond-shaped flap raised from the dorsolateral surface of the index finger to cover a defect of the first web space. The donor site is covered by an "LLL" Dufourmentel flap tailored on the dorsum of the hand avoiding a skin graft on the exposed surface of the hand.


[Radial forearm free flap with double skin island. Apropos of a clinical case].

The authors report a case of double island forearm flap for a double defect on the inferior part of the leg. The chinese flap is the only flap which has a segmental and staged vascularisation allowing multiple island skin flaps to be performed separated only by the vascular pedicle.


[Microsurgical repair after excision of large cancers. Apropos of 14 cases].

The specialty which has benefited the most from the rapid development of reconstructive microsurgery over the last decade, has been plastic surgery. In particular, the authors refer to reconstructive microsurgery after malignant tumor resection. Resections which used to cause serious psychological problems or which required multiple reconstructive procedures, can now be performed as a single stage procedure with good oncological, functional and aesthetic results. This experience concerns the treatment of 14 primary or recurrent malignant tumors of the skin and soft tissues using microsurgical techniques. The free latissimus dorsi musculocutaneous flap was the flap most commonly used. The authors also used the groin flap, the scapular flap, the tensor fasciae latae flap, the dorsalis pedis flap and finally the jejunum combined with the second metatarsus to reconstruct the mandible and the floor of the mouth. Complications consisted of complete necrosis of a dorsalis pedis flap and two revisions were performed for venous thrombosis. With a minimum follow-up of 5 years, one patient has developed a local recurrence and another has developed regional lymph node metastases. The functional and aesthetic results were quite satisfactory. The authors believe that microsurgery is a very valuable technique to treat difficult reconstructive problems.


[Breast ptosis. Classification and summary of surgical indications].

A general classification of ptotic breasts is proposed by the author in four main groups. 1) Precocious ptotic breasts including ptosis because of anomalies of skin elasticity and primary morphological ptotic aspects of the breast. 2) Ptotic breast as a result of excess of volume due to early hyperplasia, because of excess weight (around puberty, around pregnancy, around menopause). 3) Acquired ptotic small or long breast by fibrous retraction, or after weight loss. 4) Asymmetric ptotic breast, either primary, presenting at puberty or secondary presenting around pregnancy or after weight variations, or iatrogenic. An approach to the morphological analysis of each type of ptosis includes evaluation of skin quality, glandular density, relation between both. The role of weight stability is also discussed before a brief summary of the author's choice of techniques.


Thrombocytopenia in a retrovirally-induced murine erythroleukemia.

A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases.


Clinical applications of capillary electrophoresis.

Capillary electrophoresis (CE) is a new powerful separation technique that often exhibits higher resolution and shorter analysis times than high performance liquid chromatography (HPLC) or agarose electrophoresis (AE). The separation can be accomplished based on charge as well as on size, hydrophobicity, and stereospecificity. In addition to high resolution, the most significant features of CE are ease of use, low cost of operation, and the speed of the analysis thus suitable for stat work. Examples of the application of CE in the field of clinical diagnosis which are discussed include: therapeutic drug monitoring, proteins (serum, urinary and cerebrospinal fluid), and hemoglobins. This technique can reveal compounds which are not routinely analyzed in the lab thus opening a new area for the clinical investigator.


Patterns of reactivity of human anti-GM1 antibodies with spinal cord and motor neurons.

Human anti-GM1 antibodies from patients with lower motor neuron disease or predominantly motor neuropathy recognize carbohydrate determinants shared by GM1 and related glycolipids and glycoproteins, but the identity of the antigens to which they bind in tissue is unknown. We examined the binding of anti-GM1 antibodies with differing fine specificities to spinal cord, isolated motor neurons, and dorsal root ganglia neurons in order to characterize the tissue antigens. All anti-GM1 antibodies tested bound to the surface of bovine spinal motor neurons and immunostained the gray matter of unfixed sections of spinal cord. The staining was blocked by cholera toxin, which is specific for GM1, indicating that GM1 itself was the target antigen. Binding to white matter was more variable and depended on fixation and the fine specificities of the antibodies. The anti-GM1 antibodies did not bind to dorsal root ganglia neurons in tissue sections or in culture. These studies suggest that the autoantibodies might exert their effect, in part, by binding to GM1 on the surface of motor neurons, and that the absence of binding to dorsal root ganglia neurons might explain the lack of sensory abnormalities in affected patients.


Assessment of mitochondrial function in cells grown in tissue culture.

To assess mitochondrial function (pyruvate dehydrogenase [PDH] activity), cells were grown in the appropriate media to confluence, rinsed and incubated in glucose free media containing 25 microM L-lactate and [1-14C]-D,L-lactate. Lactate oxidation was measured as the amount of lactate oxidized in nmol of 14CO2 generated per mg of protein per minute. Basal activity varied with cell number and the cell type studied: fibroblast 2.26 +/- 0.01; Chinese hamster ovary (CHO) 42 +/- 0.4; BC3H-1 52 +/- 2.1 nmol per mg per minute. The CHO cells screened for PDH activity decreased their dependence on lactate as a substrate in the presence of 5mM glucose by 60 percent. Increasing the cold lactate concentration diluted the labelled lactate available for pyruvate oxidation in a dose dependent manner. The mitochondrial inhibitor rotenone (25 microM) decreased assay activity by > 75 percent in CHO and BC3H-1 cells. The lactate oxidation assay was shown to be sensitive enough to measure insulin stimulation of PDH in a dose dependent manner with maximum activity occurring at concentrations between 1 microU per ml and 100 microU per ml.


Hemoglobin C--G-Georgia double heterozygosity: a case report.

A 12-month-old black female with an unremarkable past medical history was admitted to the hospital with respiratory distress and fever without identified sepsis. Despite mechanical ventilation, the patient died as a result of respiratory insufficiency secondary to severe necrotizing bronchitis and bronchiolitis with pneumonia. Electrophoretic and biochemical analyses of the patient's hemoglobin showed the patient to be a double heterozygote for hemoglobin C (a beta chain variant) and hemoglobin G-Georgia (an alpha chain variant). This is the first report of this combination of hemoglobin variants.


Hemifacial spasm: evaluation by magnetic resonance imaging and magnetic resonance tomographic angiography.

We evaluated 37 patients with hemifacial spasm and 16 age-matched control patients with other neurological disorders using magnetic resonance (MR) imaging, MR angiography, and MR tomographic angiography. MR tomographic angiography is a new technique using computer reconstruction of MR angiographic images to create coronal angiotomes that display tissue and arterial structures on the same image. Twenty-four of 37 (64.9%) patients with hemifacial spasm had ipsilateral vascular compression of cranial nerve VII or the pons noted by this technique, whereas only 1 of 16 (6.3%) control patients had compression. MR imaging and MR angiography were less sensitive and less specific in evaluating for vascular compression. This study supports vascular compression of cranial nerve VII or the pons as a cause of hemifacial spasm, and demonstrates MR tomographic angiography's value as an excellent, noninvasive technique to demonstrate the compression.


The effect of metal chelators on lipid peroxidation in irradiated erythrocytes.

Prophylactic irradiation of blood and blood components is accepted practice in order to prevent graft-versus-host disease from infused lymphocytes. Irradiation, however, results in increased red cell potassium (K+) loss, along with other possible effects that may affect red cell function and viability. Lipid peroxidation (LP), a process initiated by the production of oxygen free radicals, is increased in red cells in the presence of reactive iron species and various heme moieties. In this report, it is noted that not only is plasma K+ significantly increased following blood irradiation, but LP is also increased compared with paired non-irradiated blood samples. Furthermore, various metal chelators significantly reduce LP in the irradiated samples. These chelators also significantly reduced the rate of cellular K+ loss during the four day 37 degrees C incubation period. This study further suggests that the addition of selected metal chelators may be effective in both irradiated and non-irradiated stored blood by improving the function and viability of transfused erythrocytes.


Magnetic resonance: a noninvasive approach to metabolism, circulation, and morphology in human brain death.

Phosphorus (31P) magnetic resonance spectroscopy and magnetic resonance imaging were used to study the intracellular metabolism, circulation, and morphology in the brains of 3 patients with clinical brain death syndrome due to traumatic brain damage, subarachnoid hemorrhage, and acute occlusive hydrocephalus caused by a colloid cyst. Magnetic resonance spectra were characterized by a complete absence of ATP and were dominated by an intense inorganic phosphate signal. Magnetic resonance imaging revealed a uniform pattern of diffuse brain swelling and tentorial and foraminal herniation. Intracranial blood flow was absent on the magnetic resonance angiography projections. These preliminary findings suggest an important impact of magnetic resonance in the determination of human brain death.


Ipsilateral fast corticospinal pathways do not account for recovery in stroke.

We tested the hypothesis that in adult humans, recovery from stroke results from the emergence of ipsilateral, fast-conducting corticospinal pathways. In 10 patients recovering from stroke, the unaffected hemisphere was stimulated with an electromagnet and changes in the firing probability of single biceps motor units were used to derive postsynaptic potentials in single biceps motoneurons. Stimuli sufficient to excite the neurons of the fast-conducting corticospinal pathway (as shown by short-latency facilitation of contralateral biceps motoneurons) did not produce short-latency depolarization of ipsilateral biceps motoneurons. The hypothesis is therefore not supported.


Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: a clinical and pathological study.

The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.


Calbindin-D28k in the basal ganglia of patients with parkinsonism.

An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D28k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin-D28k immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin-D28k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin-D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin-D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.


Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy.

Cognitive function and school achievement were studied prospectively over 3 to 4 years in 19 children treated for brain tumors with whole-brain radiotherapy; 14 of 19 also received adjuvant chemotherapy. For the group as a whole, mean IQ fell from a baseline of 104 to 92 at follow-up (p < 0.01). Age was inversely correlated with change in IQ over time (r = 0.71; p < 0.001). Children younger than 7 years at diagnosis had a mean IQ loss of 27 points, while children over 7 years at diagnosis showed no significant decrease in IQ. Decline in IQ occurred between baseline and year 2 of follow-up; none could be documented between years 2 and 4. All children younger than 7 years at diagnosis were receiving special education at follow-up; 50% of the children over 7 years at diagnosis were receiving supplemental educational services.


Amygdala cell loss and atrophy in Alzheimer's disease.

The amygdala and its subnuclei undergo severe volumetric atrophy in Alzheimer's disease (AD). To determine whether this atrophy is due to loss of neuropil, specific neuronal populations, or both, we evaluated the number, size, and packing density of neurons and glia in the cortical and magnocellular basal amygdaloid subregions. The neuropil fraction did not change with AD in either region. Despite a mean 35% increase in cell packing density in the AD amygdala, total numbers of neurons and glia within tissue sections were reduced significantly; medium and large neurons were preferentially affected. The total number of small neurons was stable in the AD sample despite sharp reductions in nuclear size, suggesting that AD also results in pronounced amygdaloid neuronal shrinkage. Differences in the degree of cell loss between the two nuclei as well as changes in glial cell numbers are discussed in relation to characteristic AD neuropathology and relevant anatomical connectivity.


Neurological intensive care.

Neurological intensive care has evolved from the principles of respiratory care established during the poliomyelitis epidemics into a broad field encompassing all of the acute and serious aspects of neurological disease. The economic and political complexities of modern intensive care play a major role in organizing a unit and building a program. Central themes of practice in modern neurological intensive care units include the clinical physiology of intracranial pressure, cerebral blood flow, and brain electrical activity; the systemic abnormalities and medical complications of nervous system diseases; postoperative care; and management of neuromuscular respiratory failure. Treatment of severe stroke and cerebral hemorrhage, brain death, ethical dilemmas of severe neurological illnesses, and the neurological features of critically ill medical patients are also becoming neurological intensive care pursuits. The "neuro-intensivist" is trained to defragment medical care by combining knowledge of neurological diseases with the techniques of intensive care. Future directions include the clinical implementation of brain resuscitation and brain-sparing therapies, sophisticated monitoring of electrophysiological and intracranial physiological indices, and further understanding of the dysfunction of other organs that follows brain and nerve failure.


The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee.

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)


Familial adult-onset muscular dystrophy with leukoencephalopathy.

We report on 3 siblings with an adult-onset, predominantly distal muscle weakness. In the female index patient this was associated with epilepsy and a progressive spastic ataxic gait, while the 2 other siblings had no appreciable clinical nervous system involvement. Additional investigations revealed muscular dystrophy and leukoencephalopathy in all 3 siblings. We conclude that this familial adult-onset muscular dystrophy associated with leukoencephalopathy represents a newly recognized autosomal recessive syndrome.


Isolated granulomatous angiitis of the spinal cord.

We describe a 31-year-old diabetic man, with granulomatous angiitis confined to the spinal cord, who developed rapidly progressive spastic paraplegia, clinically interpreted as being secondary to a spinal cord infarct. At the time of autopsy, vasculitis was limited to the spinal cord, without involvement of cerebral vessels. The inflammatory cells were predominantly CD4+ T lymphocytes, with few CD8+ T and B lymphocytes. The phenotypical composition of the inflammatory infiltrate is similar to that described in other granulomatous disorders such as sarcoidosis and tuberculin reaction.


Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease.

L-Carnitine and acetyl-L-carnitine facilitate mitochondrial beta-oxidation of fatty acids. In the brain, they may also have a role in acetylcholine synthesis. Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine. Recently, acetyl-L-carnitine was reported to have a beneficial effect in patients with Alzheimer's disease. We therefore assessed carnitine acetyl-transferase activity in selected brain regions and in isolated cerebral microvessels obtained at autopsy from patients with Alzheimer's disease and from age-matched control subjects. We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels. These findings document another neurochemical abnormality in patients with Alzheimer's disease and provide a rationale for the use of acetyl-L-carnitine in the treatment of patients with Alzheimer's disease.


Extraocular muscles are spared in advanced Duchenne dystrophy.

Fast-twitch extremity muscle fibers are preferentially affected in Duchenne's and Becker's muscular dystrophy. Since saccades are thought to be mediated by fast-twitch fibers, saccadic velocities would be expected to be decreased in these patients. Using infrared oculography, we found that the peak velocities of saccades in 3 patients with advanced Duchenne's or Becker's muscular dystrophy were normal. Clinical findings in 7 other patients with these forms of dystrophy were normal. This investigation is the first study of ocular motility in Duchenne's and Becker's muscular dystrophy. It demonstrates that extraocular muscle function is preserved and suggests that fast-twitch fibers in extraocular muscles possess properties that protect against degeneration.


Alpha-tocopherol levels in brain are not altered in Parkinson's disease.

alpha-Tocopherol (vitamin E) levels in normal brain were lower in the cerebellum than in the cerebral cortex or basal ganglia. There was no difference in alpha-tocopherol levels in the cerebellum, basal ganglia, or cerebral cortex between control subjects and patients with Parkinson's disease.


Photodynamic therapy for the treatment of basal cell carcinoma.

Photodynamic therapy is an investigational method for the treatment of a variety of solid tumors. The purpose of this study was to determine the optimum factors and illustrate the effectiveness of photodynamic therapy in the treatment of basal cell carcinomas. This was a prospective study in which patients presenting with primary or recurrent basal cell tumors, particularly but not exclusively widespread tumors or large single tumors, were offered the option of photodynamic therapy in their treatment regimen. Patients were administered 1 mg/kg of a photosensitizer (Photofrin II). Light doses (630 nm) ranged from 72 to 288 J/cm2. A total of 37 patients with 151 sites were treated in this study. A complete response rate of 88% was achieved with one application. Morbidity was low; the most significant side effects were moderate pain and edema. Photodynamic therapy is a modality that offers localized treatment of primary or recurrent nonmelanoma skin cancer. By applying reciprocal doses of photosensitizer and light, the efficacy of photodynamic therapy in the treatment of skin lesions is demonstrated achieving significant light penetration into tissue with a high complete response rate of the lesions and acceptable normal tissue response.


Frequency and prognostic significance of clonal T-cell receptor beta-gene rearrangements in the peripheral blood of patients with mycosis fungoides.

Previous studies have shown that peripheral blood involvement is a poor prognostic sign in patients with cutaneous T-cell lymphoma. However, evaluation of the results of these studies is difficult. In this study peripheral blood mononuclear cells from 45 patients with various stages of mycosis fungoides (MF) were investigated for the presence of clonal T-cell populations by T-cell receptor beta (TCR beta)-gene rearrangement analysis. Clonal TCR beta-gene rearrangements were found in five (11%) of 45 patients with MF, including one (3%) of 31 patients without MF and four (27%) of 15 patients with histologically confirmed lymph node involvement. With respect to skin stage, clonal T-cell populations were detected in one (4%) of 23 patients with plaque stage disease, two (10%) of 19 patients with tumor stage disease, and two (50%) of four patients with erythrodermic MF. In the group of patients with lymph node involvement the median survival of patients with detectable clonal T-cell rearrangements in the peripheral blood was much shorter (3 months) than that of patients without clonal rearrangements (16 months). The results of this study indicate that clonal TCR beta-gene rearrangements, as detected by Southern blot analysis, are uncommon in the peripheral blood of patients with MF, in particular in patients without histologically documented lymph node involvement. The presence of clonal T-cell populations in the peripheral blood of MF patients with lymph node involvement is usually associated with rapidly fatal disease.


The incidence and prevalence of dermatitis herpetiformis in Utah.

The incidence and prevalence of dermatitis herpetiformis has never been formally evaluated in any area of the United States. Several northern European studies have shown prevalence rates ranging from 1.2 per 100,000 to 39.2 per 100,000. The present study was performed to evaluate the incidence and prevalence of dermatitis herpetiformis in Utah. Information from 240 patients diagnosed with dermatitis herpetiformis was compiled from hospital records throughout Utah, as well as the sole private dermatopathologist in the state, and from the university referral center of the state. Criteria for inclusion in the study were a clinical diagnosis of dermatitis herpetiformis plus granular deposition of IgA in dermal papillae by direct immunofluorescence of uninvolved skin, or histopathologic findings consistent with the disease. Clinical diagnosis and response to dapsone alone was considered insufficient for inclusion in the study. On the basis of these criteria, as well as exclusion of non-Utah residents, 188 of the original 240 patients qualified for the study. The prevalence of dermatitis herpetiformis in Utah in 1987 was 11.2 per 100,000. The mean incidence for the years 1978 through 1987 was 0.98 per 100,000 per year. The mean age at onset of symptoms for male patients was 40.1 years, and that for female patients was 36.2 years. The male-female ratio was 1.44:1. This represents the first evaluation of the incidence and prevalence of dermatitis herpetiformis in the United States. These results are similar to those of the previous studies, probably because of Utah's largely northern European ancestry. This population base, plus a much smaller than average black and Oriental population, is likely to have produced a higher incidence and prevalence in Utah than would be seen in other areas of the United States.


Pyoderma faciale. A review and report of 20 additional cases: is it rosacea?

Pyoderma faciale was originally described by O'Leary and Kierland in 1940. It is characterized by the sudden onset of monstrous coalescent nodules and confluent draining sinuses confined to the face of young women in their early 20s. This report summarizes our results in 20 cases. The women were 15 to 46 years old (mean, 25 years). All women were flushers and blushers. Histopathologic examination revealed a dense perivascular and periadnexial infiltrate, including granulocytes, eosinophils with epithelioid granulomas, and septal and lobular panniculitis. No consistent laboratory abnormalities were found. After much therapeutic experimentation, we developed an effective treatment plan, based on a combination of oral isotretinoin and corticosteroids. We regard it as an extreme form of rosacea and suggest it be renamed rosacea fulminans in analogy with its counterpart, acne fulminans.


Q-switched ruby laser therapy of nevus of Ota.

The Q-switched ruby laser has been demonstrated to provide selective photothermolysis of pigmented tissue at a wavelength of 694 nm and a pulse width of 40 ns with dermal penetration. It was used to treat 15 patients with nevus of Ota involving the face with an age range of 6 to 52 years. Other methods of treatment for the nevus of Ota have either left scarring or were ineffective. The clinical efficacy of this laser treatment was evaluated in a comparative photographic analysis. Complete clearing was noted in four of the 15 patients and a minimum of 50% lightening of the original color in the remaining 11. Ten of the 15 patients were Asian, two were white, two were Hispanic, and one was Indian. The energy fluence used varied between 6 and 10 J/cm2, and the number of treatments ranged from 1 to 7. Significant lightening or clearing was found at the higher energy ranges of 9 to 10 J/cm2 with significantly less lightening noted at the lower energy range of 6 to 8.5 J/cm2. No scarring was noted in any of the 15 patients, and some isolated hypopigmentation was noted in one of the subjects. Transient postinflammatory hyperpigmentation of 2 months' duration was noted in only one patient. Q-switched ruby selective photothermolysis appears to be an effective and safe method of lightening or removing nevus of Ota.


Pharmacologic treatment of severe skin-picking behaviors in Prader-Willi syndrome. Two case reports.

Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Other behavioral symptoms that become prominent during adolescence and adulthood include temper outbursts, stealing and hoarding food, and skin picking. The self-excoriating skin picking behavior observed in individuals with PWS is quite common and can lead to persistent sores and infections, even requiring hospitalization. Two patients with PWS who displayed repetitive, self-mutilatory behavior of skin picking are described. They were both treated successfully with different doses of fluoxetine, a selective serotonin reuptake inhibitor. The skin-picking behavior in patients with PWS may be a variant of the spectrum of obsessive-compulsive disorders. Obsessive-compulsive disorders have been successfully treated with serotonin reuptake inhibitors such as fluoxetine. Thus, fluoxetine may be considered an option in the management of skin-picking behavior in patients with PWS.


Treatment of pemphigus vulgaris with pulse intravenous cyclophosphamide.

Although corticosteroids have dramatically altered the prognosis in pemphigus vulgaris, morbidity and mortality from systemic corticosteroid side effects remains high. While immunosuppressive agents have been successfully used in pemphigus vulgaris, there is a high incidence of side effects with these agents as well. Particularly bothersome are reports of increased risk of malignancy with long-term use of immunosuppressive agents. For these reasons, we used a protocol that includes low-dose oral cyclophosphamide coupled with pulse intravenous cyclophosphamide in two patients with recalcitrant pemphigus vulgaris. Both patients responded well to monthly doses of intravenous cyclophosphamide with rapid decrease in the frequency and severity of blistering, resulting in resolution of their disease after 7 and 10 months, respectively. Pulse doses of immunosuppressive agents appear to be successful in the treatment of pemphigus vulgaris. High-dose steroid therapy can be tapered with the use of this treatment. Because monthly intravenous doses of cyclophosphamide lead to a substantially reduced cumulative dose, when compared with standard oral regimens, the risk of developing malignancy may also be reduced. Further studies using larger groups of patients are needed to evaluate the efficacy of pulse intravenous cyclophosphamide in pemphigus vulgaris. Long-term follow up will be necessary to compare the incidence of malignancy in patients receiving pulse doses of immunosuppressive agents with that in patients receiving continuous oral treatment.


Field evaluation of coverall fabrics: heat stress and pesticide penetration.

The effect of wearing coveralls on the heat stress of ten professional airblast applicators of ethion to Florida citrus were studied. During the period June 21, 1988 to August 9, 1988, applicators wore protective clothing of the same design, but made of seven different fabrics. Heat stress was evaluated by measuring the mean skin temperature, oral temperature, and heart rate of pesticide applicators. Subjects also provided subjective evaluations. Seven environmental variables were also monitored. Although each fabric was replicated an average of 17 times for thermal comfort and an average of 23 times for penetration, statistical tests for differences among fabrics were usually not significant at the p less than 0.05 level. Observed differences among suits were statistically significant at p = 0.27 for the heat stress experiment, and extended over the range p = 0.003-0.500 for the penetration experiment. Lighter weight, untreated fabrics marginally ameliorated heat stress under severe environmental conditions, but they allowed more pesticide penetration.


Small area pesticides data: multiplicity and variability of pesticide usage on southern row crops.

Epidemiologic studies of possible effects of agricultural environments upon human health suffer from lack of reliable pesticides usage data. The Arkansas Reproductive Health Monitoring System has developed a method for estimating specific pesticides usage annually for sub-county regions, including amounts, application method, and months. This method is applied to 39 regions of 8 central Arkansas counties for 1980-82. The hugh variability of pesticides usage on individual crops demonstrates the inaccuracy likely if general survey estimates are employed. Annual usage of pesticides in a single sub-county region of 53,000 hectares (130,880 land acres) was greater than 1/2 million pounds (248,670 kg) of 60 pesticides, 40 of which were applied during a four month period. The multiplicity and variability of pesticides usage indicate the need for locally developed pesticides data for epidemiologic studies and for combined studies across regions with widely differing agricultural practices.


Reproductive output of a meiobenthic copepod exposed to sediment-associated fenvalerate.

The benthic harpacticoid copepod, Amphiascus tenuiremis, was cultured through one generation at four concentrations (600, 300, 150, and 0 micrograms/kg) of sediment-associated fenvalerate, a synthetic pyrethroid insecticide, to assess effects on reproductive output and age structure. Two static renewal experiments with four replicates of each treatment were conducted. At the end of 21 days, surviving copepods were sorted and counted into adult males, adult females, copepodites, and nauplii. Fenvalerate was extracted from the sediment and measured by GC-MS. The number of individuals in each life-history stage in fenvalerate treatments was not significantly different from controls, except for increased adult females in fenvalerate in the second experiment. The overall lack of a fenvalerate toxic effect on A. tenuiremis was most likely because fenvalerate tightly binds to sediments and was probably not bioavailable to the copepods. Sediment-associated pesticides with large octanol:water partitioning coefficients (K(ow)'s) such as fenvalerate appear to be less toxic to infaunal copepods than those exhibiting smaller K(ow)'s.


Effects of 2,4-dichlorophenoxyacetic acid on Rhizobium sp. membrane fluidity.

The effects of 1 mM 2,4-Dichlorophenoxyacetic acid on Rhizobium sp. in pure culture was studied. In a previous work it was demonstrated that this herbicide produces an alteration on the saturated to unsaturated phospholipid acyl chains ratio. In the present paper, it was found that this alteration produces a modification on the membrane fluidity in bacteria that had achieved the stationary phase. The same results were obtained when determinations were done in liposomes from sonicated lipids of treated bacteria, indicating that changes in phospholipid acyl chains may be the main cause of membrane fluidity alteration. In addition, it was determined that leucine transport as well as Ca(++)-ATPase activity (a membrane enzyme) was affected under the experimental conditions.


Oxidative changes in brain of aniline-exposed rats.

Oxidative stress in rat cerebellum, cortex and brain stem after a short-term high-dose exposure to aniline vapors under conditions akin to those after major chemical accidents, was studied. Significant increases in superoxide dismutase isozyme activities and formation of thiobarbituric acid reactive material along with depletion of ascorbic acid and non-protein sulfhydryl content suggest impairment of antioxidant defenses 24 h after single exposure to 15,302 ppm aniline vapors for 10 min.


Benzo(a)pyrene-blood protein adducts in wild woodchucks used as biological sentinels of environmental polycyclic aromatic hydrocarbons contamination.

Levels of benzo(a)pyrene-diolepoxide (BaPDE)-albumin and BaPDE-hemoglobin adducts in wild woodchucks (Marmota monax) have been measured to evaluate the potential usefulness of these parameters in the assessment of environmental contamination by polycyclic aromatic hydrocarbons (PAHs). Blood was obtained from nine woodchucks living near an aluminum electrolysis plant, contaminated area (Saguenay region, Québec, Canada), and from eight living in a control area (Saint-Roch-des-Aulnaies, Québec, Canada). Blood samples were collected and plasma separated from red blood cells by centrifugation on site. Isolation of albumin (Alb) and hemoglobin (Hb) was performed in our laboratory and each protein fraction was subjected to mild acid hydrolysis yielding free benzo(a)pyrene (BaP) tetrol from the adducts. The analysis was performed by high performance liquid chromatography (HPLC) using fluorescence detection. For the control and contaminated areas geometric mean (interval) Alb adduct levels were 7.6 (0.8-29.3) and 69.6 (10.0-1,103) pmol tetrol/g protein (p less than 0.01) while the corresponding figures for Hb adduct levels were 0.40 (0.01-2.72) and 1.18 (0.02-12.8) pmol/g protein (p greater than 0.01). Alb but not Hb adduct levels were associated with the measured concentration of BaP in the vegetation samples collected on the site where each animal was found. This is compatible with the short half-life of Alb adducts and with the instantaneous image provided by BaP measurements in the collected vegetation samples. BaPDE-blood protein adducts measured in wild animals appear to be good biomarkers of environmental contamination by PAHs.