Bilateral bispectral index monitoring during suppression of unilateral hemispheric function

Bispectral Index (BIS) has been used to monitor level of "sedation" based on the electroencephalogram (EEG). Patients evaluated for surgery to control a seizure disorder undergo Wada testing, during which one hemisphere is rendered functionally inactive after injecting a short-acting barbiturate. We surmised that the BIS values would reflect these functional changes. Eight epileptic patients were enrolled. A full array of 21 EEG electrodes and 2 BIS XP (Quatro) strips over each frontal region of the scalp were applied. The EEG was continuously recorded. BIS values from each hemisphere were recorded every minute. Angiography was performed by advancing a catheter into each internal carotid artery. Amobarbital or methohexital was injected until the patient developed a hemiparesis. The EEG confirmed a significant lateralized cortical effect of the barbiturate. Repeated measures analysis of variance was used to analyze the differences between the BIS values from monitor electrode strips placed on the left (left BIS) and the right (right BIS) sides of the head as well as the differences in the left and right BIS values before and after each injection of the barbiturate. Injection of barbiturate into either the left or right internal carotid artery produced a significant change on the 21-electrode EEG. However, there was no difference between left BIS to right BIS values (P = 0.84). With repeated injections of barbiturates, some patients became sedated. At these times, both left BIS and right BIS values decreased together before and after injection of barbiturate. The BIS monitor was unable to distinguish significant hemispheric EEG and clinical functional changes except when the patient became sedated.     

Modulatory Effect of Isoprinosine on Lymphocyte Proliferative Response Under Immunodeppressive Conditions

In the present work the effect of Isoprinosine on the mitogenic responses of T and B lymphocytes has been studied. We have found that Isoprinosine can enhance in vitro the response to Concanavalin A. This enhancement was more apparent in cell cultures showing an initially low blastogenic response. In low responses artificially induced by treatments in vivo with cyclophosphamide, our results indicate that Isoprinosine, administered in vivo, does not enhance the response to Con A of treated mice. However, addition of Isoprinosine (75 μg/ml) to cultures of spleen cells from mice previously treated with cyclophosphamide enhanced the suppressed response up to normal levels. Neither in vivo nor in vitro Isoprinosine treatments increased the response of lymphocytes to lipopolysaccharide, but usually inhibited the blastogenesis of B cells.     

Pulmonary applications of perfluorochemical liquids: ventilation and beyond

In this review of liquid ventilation, concepts and applications are presented that summarise the pulmonary applications of perfluorochemical liquids. Beginning with the question of whether this alternative form of respiratory support is needed and ending with lessons learned from clinical trials, the various methods of liquid assisted ventilation are compared and contrasted, evidence for mechanoprotective and cytoprotective attributes of intrapulmonary perfluorochemical liquid are presented and alternative intrapulmonary applications, including their use as vehicles for drugs, for thermal control and as imaging agents are presented.     

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

Abnormal neuronal cytoplasmic inclusions (NCIs) containing aggregates of -internexin and the neurofilament (NF) subunits, NF-H, NF-M, and NF-L, are the signature lesions of neuronal intermediate filament (IF) inclusion disease (NIFID). The disease has a clinically heterogeneous phenotype, including frontotemporal dementia, pyramidal and extrapyramidal signs presenting at a young age. NCIs are variably ubiquitinated and about half of cases also have neuronal intranuclear inclusions (NIIs), which are also ubiquitinated. NIIs have been described in polyglutamine-repeat expansion diseases, where they are strongly ubiquitin immunoreactive. The fine structure of NIIs of NIFID has not previously been described. Therefore, to determine the ultrastructure of NIIs, immunoelectron microscopy was undertaken on NIFID cases and normal aged control brains. Our results indicate that the NIIs of NIFID are strongly ubiquitin immunoreactive. However, unlike NCIs which contain ubiquitin, -internexin and NF epitopes, NIIs contain neither epitopes of -internexin nor NF subunits. Neither NIIs nor NCIs were recognised by antibodies to expanded polyglutamine repeats. The NII of NIFID lacks a limiting membrane and contains straight filaments of 20 nm mean width (range 11–35 nm), while NCIs contain filaments with a mean width of 10 nm (range 5–18 nm; t-test, P<0.001). Biochemistry revealed no differences in neuronal IF protein mobilities between NIFID and normal brain tissue. Therefore, NIIs of NIFID contain filaments morphologically and immunologically distinct from those of NCIs, and both types of inclusion lack expanded polyglutamine tracts of the triplet-repeat expansion diseases. These observations indicate that abnormal protein aggregation follows separate pathways in different neuronal compartments of NIFID.     

In vivo feasibility of image-guided transvaginal focused ultrasound therapy for the treatment of intracavitary fibroids

OBJECTIVE: To determine the feasibility of uterine tissue ablation in vivo using a transvaginal focused ultrasound applicator guided by ultrasound imaging. DESIGN: Randomized in vivo animal study. SETTING: Academic research environment. ANIMAL(S): Healthy anesthetized sheep. INTERVENTION(S): Uterine treatment location was determined using a computerized targeting system. Five sonications 10 seconds in duration and averaging 2,000 W/cm(2) of focal ultrasound intensity were applied in each animal's uterus. Animals were euthanized either immediately or 2, 7, or 30 days post-treatment. MAIN OUTCOME MEASURE(S): Gross and microscopic analysis of the dissected uterus was used to quantitatively and qualitatively determine the ablated region and treatment side effects. RESULT(S): Treatments resulted in coagulative necrosis. Histopathological analysis showed that over 7 days, inflammatory cells appeared and smooth muscle bundles regenerated. By day 30, treated tissues healed and scar tissue formed. None of the animals showed abnormal behavior or medical problems. Complications in three animals were damage to the vaginal wall and colon, possibly due to inadequate applicator cooling and an empty bladder during treatment. CONCLUSION(S): Transvaginal image-guided high-intensity focused ultrasound has potential for treating uterine fibroids. Further safety testing of this treatment will prepare it for human use.     

Pilonidal Sinus -- Primary Closure also in Case of Abscess?

After excision of pilonidal sinus treatment consists either in open procedure or primary closure. We present the results of 45 consecutive patients (male 29, female 16, age 32 +/- 13 years), who underwent surgery between September 2001 and December 2002. Fourteen patients had simple fistula without infection, 18 had fistulas with putride secretion and 13 had abscess. Primary closure with direct suture was performed in 34 patients (76 %: 13 x simple fistula, 13 x fistula with putride secretion, 8 x abscess). Eleven patients were treated by layopen procedure and secondary wound healing. Wound infection occurred in 13 patients (7 x superficial, 6 x deep). Mean time of postoperative treatment was 15 +/- 3 days after closure and primary healing and 66 +/- 15 days after open proce dure or secondary healing. Mean time out of work was 19 +/- 10 respectively 52 +/- 19 days. A recurrence of fistula occurred in eight patients after primary closure (18 %) and none after open procedure. Also in cases of pilonidal sinus with infection, primary wound closure can be carried out even though the rate of recurrences is higher than after open procedure. A successful primary closure significantly reduces time of illness and time out of work.     

Early hepatic nodular hyperplasia and submicroscopic fibrosis associated with 6-thioguanine therapy in inflammatory bowel disease

BACKGROUND: 6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (IBD) patients not responsive to or intolerant of azathioprine (AZA) and 6-mercaptopurine (6-MP). 6-TG-related hepatotoxicity, including liver biochemistry value elevations, sinusoidal collagen deposition on electron microscopy, and veno-occlusive disease, have been described related to its use as therapy for neoplastic disease. METHODS: We studied 38 liver biopsies from patients treated with 6-TG, almost all of whom (n = 125) received 6-TG for 1 to 3 years at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. All biopsies were fixed in 4% buffered formalin and prepared in the usual manner. Hematoxylin and eosin, Masson's trichrome (trichrome), and reticulin silver impregnation (reticulin) stained slides were studied. In 23 cases, tissue was also prospectively fixed in glutaraldehyde and processed for electron microscopy. RESULTS: In 20 of the 37 patients studied (53%), nodular regeneration of varying degree was seen with reticulin. In only 4 of these 20 instances (11% of the total) were the changes seen with hematoxylin and eosin and in 3 of the 4, only in retrospect after studying the reticulin preparation. Minimal fibrosis was seen with trichrome in only 13 biopsies (34%), but sinusoidal collagen deposition was observed in 14 of the 23 cases studied with electron microscopy (60%). The biopsy from the 1 patient with nodular hyperplasia obvious with hematoxylin and eosin also demonstrated changes of venous outflow obstruction. CONCLUSIONS: 6-TG-treated IBD patients are at significant risk for nodular hyperplasia, early fibrosis and, less often, venous outflow disease (Budd-Chiari). The natural history of these changes is unknown and follow-up biopsies are needed to determine histologic and clinical sequela. Patients not demonstrating nodular hyperplasia or fibrosis who continue with 6-TG because there are no better therapeutic choices should be periodically rebiopsied.     

Increased kidney growth in formula-fed versus breast-fed healthy infants

A high protein intake results in increased kidney growth and glomerular filtration rate in human adults and young rats. It is unknown whether kidney size in young infants is influenced by increased protein intake in formula-fed compared with breast-fed infants. We investigated the effect of formula versus breast feeding on kidney growth in a cohort of 631 healthy children examined at birth, and at 3 and 18 months of age. Kidney size was determined by ultrasonography and related to gender, age, body size, and feeding category (fully breast fed, partially breast fed, or fully formula fed at 3 months). Serum urea nitrogen, serum creatinine, and estimated creatinine clearance were measured at 3 months of age. Kidney growth and serum urea nitrogen were significantly increased in partially or fully formula-fed 3-month-old infants. This effect was more pronounced in boys than in girls. The changes in relative kidney size were temporary, as they did not persist at 18 months of age, when all children received a normal mixed diet. The immediate renal effects of formula feeding should be taken into consideration for recommendations concerning infant feeding. Whether there are any long-term effects of early increased protein intake on later kidney function remains to be seen.