Effect of flunixin meglumine and cimetidine hydrochloride on the pH in the third compartment of the stomach of llamas.

A Tigon fistula was surgically implanted into the third compartment of the stomach of 5 llamas to allow measurement of gastric pH. The llamas were allotted into 2 groups and given flunixin meglumine or cimetidine hydrochloride for 3 days. After 4 days without treatment, the drugs given to each group were reversed. Measurements of gastric pH were taken every 30 minutes for 6 hours, using an automated pH meter. The pH measurements after drug administration were compared with measurements obtained during a pretreatment control period. Gastric pH during pretreatment control periods had a mean of 1.43 +/- 0.063 (mean +/- SE). The use of flunixin did not significantly decrease gastric pH, compared with pretreatment controls. Gastric pH was significantly higher within the first 30 minutes after administering cimetidine, compared with pretreatment controls, but this difference disappeared at all later times.


Abomasal luminal pressure in cattle with abomasal volvulus or left displaced abomasum.

The abomasal luminal pressure was determined during surgery in 54 dairy cows with abomasal volvulus (AV) and another 50 dairy cows with left displaced abomasum. The luminal pressure was high in all cattle with AV and 49 (98%) cattle with left displaced abomasum. Luminal pressure was significantly higher in cattle with AV (median, 11.7 mm of Hg; range, 4.1 to 32.4 mm of Hg) than cattle with left displaced abomasum (median, 8.7 mm of Hg; range, 3.5 to 20.7 mm of Hg). Among cattle with AV, abomasal luminal pressure was significantly higher in cattle that died or were sold for slaughter following surgery (median, 20.6 mm of Hg; n = 8) than in cattle that were retained in the herd (median, 11.0 mm of Hg; n = 46). The luminal pressure was weakly correlated with the preoperative serum alkaline phosphatase activity but not correlated with duration of inappetence before surgery. Calculation of likelihood ratios and construction of a response operating characteristic curve for cattle with AV indicated that a cut-off value of 16 mm of Hg for luminal pressure optimized the distribution of cattle into productive and nonproductive groups. The sensitivity, specificity, positive predictive value, and negative predictive value of a luminal pressure < 16 mm of Hg in predicting a productive outcome were 0.83, 0.75, 0.95, and 0.43, respectively.


Inherited phosphofructokinase deficiency in an American cocker spaniel.

A 3-year-old female American Cocker Spaniel with a chronic hemolytic disorder and hemolytic crises was found to have M-type phosphofructokinase deficiency. This inherited erythroenzymopathy and myopathy is commonly diagnosed in English Springer Spaniels, but the family study of this Cocker Spaniel, although supporting an autosomal recessive mode of inheritance, did not reveal any English Springer Spaniel ancestors. Molecular genetic studies did, however, identify the same mutation in this dog as we previously reported in the English Springer Spaniel breed, suggesting that this mutation originated prior to the separation of these 2 breeds.


Acute sterile hemorrhagic cystitis after a single intravenous administration of cyclophosphamide in three dogs.

Three dogs receiving cyclophosphamide IV as part of a combination chemotherapeutic regimen developed macrohematuria, stranguria, and pollakiuria within 24 hours of administration of the first dose of this drug. An 11-year-old spayed mixed-breed dog with an oral squamous cell carcinoma was administered 250 mg of cyclophosphamide/m2 of body surface, whereas a 4-year-old castrated male Gordon Setter was treated with 100 mg of cyclophosphamide/m2 and a 6-year-old male German Shepherd Dog with a cutaneous hemangiosarcoma was administered 140 mg of cyclophosphamide/m2. Aerobic bacterial culture, antimicrobial susceptibility testing, and urinalysis were performed on urine obtained by cystocentesis from all 3 dogs after hematuria was observed. Sterile hemorrhagic cystitis was diagnosed on the basis of large numbers of RBC in the urine, lack of pathogens on bacterial culturing of urine, and clinical signs. Although cyclophosphamide-induced cystitis in dogs has been reported in the literature numerous times, acute episodes developing within 24 hours of administration of the first dose have not been reported in this species with the use of therapeutic doses. Therefore, appropriate precautionary steps should be taken, even when the drug is being administered intermittently.


Clinical, echocardiographic, and Doppler imaging characteristics of mitral valve stenosis in two dogs.

Mitral stenosis was diagnosed noninvasively by echocardiography and Doppler imaging in 2 Bull Terriers. Two-dimensional echocardiography revealed severe atrial and moderate left ventricular dilatation; severely reduced mitral valve opening excursion; doming of the cranial mitral valve leaflet into the left ventricle during diastole; thickened, nodular cranial mitral valve leaflets; and reduced mitral valve orifice. M-mode echocardiographic findings additionally indicated greatly diminished mitral valve E to F slope and abnormal caudal mitral valve leaflet motion. Color flow Doppler imaging revealed bright bursts of color with aliasing originating from the stenotic mitral valve orifice, extending into the left atrium during systole, and into the left atrium during diastole. Spectral Doppler recordings revealed transvalvular mitral valve gradients and prolonged pressure half-times. Necropsy performed on 1 dog revealed extremely thickened, nodular, and stiff mitral valves with short, thickened, and fused chordae tendineae. The diagnosis of mitral valve stenosis was easily facilitated with diagnostic ultrasonography.


Phenobarbital-responsive episodic dyscontrol (rage) in dogs.

Episodic dyscontrol (rage) was diagnosed from the clinical history, electroencephalographic findings, and response to oral treatment with phenobarbital in 3 dogs. Clinical features included a mood change heralding aggressive incidents, explosive aggression directed at people or objects, and a postaggressive phase characterized by lethargy and lack of responsiveness. Abnormal electroencephalographic findings included spike activity in the temporal recordings. All 3 dogs responded well to anticonvulsant medication with phenobarbital.


Surgical correction of urethral dilatation in an intersex goat.

Multiple congenital urethral abnormalities were successfully corrected in a polled goat kid. Anatomic genito-urinary abnormalities identified were paired testes with associated epididymis, ductus deferens, and active endometrial tissue. Blood karyotyping revealed the female state--XX sex chromosomes. This case exemplifies the complex interactions in addition to Y dominant Mendelian genetics that determine reproductive tract development in goats. The resultant intersex state is clinically recognized with greater frequency in polled progeny.


Use of an implant for intraosseous infusion as supportive therapy for a Vietnamese pot-bellied pig with urethral obstruction caused by a polyp.

A Vietnamese pot-bellied pig with a urethral polyp was supported by total parenteral nutrition given through an intraosseous implant. Peripheral vascular access was difficult to establish and maintain in this anorectic pig, so a pediatric intraosseous implant was placed in the left tibia. Surgical repair of the urethra was not considered possible, and alternative techniques of a functional bypass were unacceptable to the owners, so euthanasia was elected. Histologic examination of the urethra revealed a polypoid structure believed to be similar to benign congenital polyps described in young boys.


Cryptococcal pneumonia and abortion in an equine fetus.

Cryptococcus neoformans was the causative agent of pneumonia in a 9-month-old equine fetus aborted by a healthy American Paint mare. Endometritis was diagnosed on biopsy, and vaginal specimens obtained for culture were Cryptococcus-positive 1 month following abortion but not 5 months after abortion. Infection resolved without treatment between 1 and 5 months after abortion, and the mare was bred the following year and delivered a live premature foal without evidence of Cryptococcus infection.


Idiopathic, aseptic, effusive, fibrinous, nonconstrictive pericarditis with tamponade in a standardbred filly.

A Standardbred filly was admitted for evaluation of pleuritis and pneumonia. Heart rate was 80 to 120 beats/min, and the pulse was barely palpable. Thoracic and abdominal ultrasonography and echocardiography revealed substantial pericardial effusion with cardiac tamponade, fibrinous pericarditis, pleural effusion, and ascites. Initial electrocardiography revealed normal sinus rhythm with decreased amplitude of the QRS complexes consistent with pericardial effusion. Following thoracentesis, echocardiogram-guided pericardiocentesis was performed. Bacterial culture yielded no growth from any of the fluids, and bacteria were not seen on cytologic examination. Initial treatment included broad-spectrum antibiotic treatments, IV fluid therapy, and anti-inflammatory agent administration. On the basis of negative culture results, an immune-mediated cause was considered, and dexamethasone was instituted in a decreasing dosage regimen. Pericardial effusion, ventral edema, and ascites began to resolve within 3 days after beginning dexamethasone treatment. Thirty days following discharge, the filly was reexamined, and at that time, the prognosis for athletic performance was considered good so the horse was returned to race training. The final diagnosis in this case was idiopathic, effusive, nonconstrictive pericarditis with tamponade. Early identification, clinical understanding, and application of knowledge of the pathophysiologic mechanisms of pericarditis in horses, combined with use of diagnostic aids such as ultrasonography and aggressive therapy consisting of effusion drainage, pericardial lavage, antibiotics that penetrate the pericardium, and corticosteroids when indicated are critical for a successful outcome in horses with pericarditis.


Hypothyroidism in a scarlet macaw.

A diagnosis of hypothyroidism was confirmed by use of thyrotropin stimulation testing in an imported male scarlet macaw. Clinical signs included delayed molt; uniform, diffuse contour feather loss over the entire body; and excessive fat deposition over the legs and ventral portion of the abdomen. Clinical signs were associated with mild, non-regenerative anemia; mild leukocytosis; heterophilia; hypoalbuminemia; and hypercholesterolemia. Histologic examination of punch biopsy specimens from regions of feather loss revealed ortho- and parakeratotic hyperkeratosis of the epidermis and moderate, widespread vacuolar degeneration and necrosis in the follicular epithelium. The bird failed to respond to provocative thyrotropin stimulation testing. Treatment with L-thyroxine (0.2 micrograms/kg of body weight, q 12 h) resulted in normal feathering, elimination of fat deposits, and adequate serum thyroxine concentrations at 4 and 12 hours after treatment.


Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990).

Idiopathic inflammatory bowel disease was the diagnosis for 58 dogs and 26 cats, with signs of persistent gastroenteritis, failed responses to dietary trials, and histologic evidence of cellular infiltrates unrelated to other causes of gastrointestinal tract inflammation. Clinical signs of large intestinal dysfunction, watery diarrhea, vomiting, and anorexia with weight loss were common. Nonspecific hematologic, biochemical, and radiographic abnormalities frequently were observed. Mucosal biopsy specimens, obtained endoscopically, were histologically evaluated for severity of mucosal epithelial damage. Mucosal erythema, friability, enhanced granularity, and ulceration or erosion were the predominant endoscopic lesions. Inflammatory bowel disease lesions of moderate severity predominated in the stomach, duodenum, and colon. Lymphocytic/plasmacytic infiltrates were limited to the lamina propria in biopsy specimens from all regions of the gastrointestinal tract. Inflammatory bowel disease commonly is associated with chronic gastroenteritis in dogs and cats.


Coccidioidomycosis in llamas in the United States: 19 cases (1981-1989).

Coccidioidomycosis was diagnosed in 19 llamas (California, 9; Arizona, 10). All but 1 had a disseminated form, with pyogranulomas principally in the lungs, thoracic lymph nodes, liver, and kidneys. However, lesions were found in tissue specimens from most organ systems. Antemortem diagnosis was based on radiographic evaluation of the lungs, serologic testing, or presence of spherules of Coccidioides immitis in pyogranuloma aspirates, skin scrapings, or biopsy specimens. Animals residing in endemic areas of southwestern United States are at risk, and llamas appear to be highly susceptible to developing disseminated forms of coccidioidomycosis.


Pneumonia associated with Salmonella choleraesuis infection in swine: 99 cases (1987-1990).

Salmonella choleraesuis was isolated in pure or mixed bacterial cultures from 153 swine necropsied between Jan 1, 1987 and Dec 31, 1990. Pneumonia was seen in 99 of 109 swine from which this bacterium was isolated in the absence of other pathogenic bacteria. Pneumonia was seen more frequently than hepatitis, splenomegaly, or colitis. Pleuropneumonia that was grossly indistinguishable from the pleuropneumonia associated with Actinobacillus pleuropneumoniae was seen in 29 of 99 swine from which S choleraesuis was the only bacterium isolated.


Novel membrane proteins present in teicoplanin-resistant, vancomycin-sensitive, coagulase-negative Staphylococcus spp.

Clinical isolates of Staphylococcus epidermidis and Staphylococcus haemolyticus resistant to teicoplanin (MIC 64 mg/L) and sensitive to vancomycin (MIC 2 mg/L), were compared with vancomycin- and teicoplanin-sensitive isolates (MICs 1 mg/L) of the same species. No apparent differences between the sensitive and resistant strains of either pair were found with respect to binding of teicoplanin to the bacteria, or to the amino acid content or degree of cross-linkage of purified peptidoglycan. The resistant strains did not inactivate teicoplanin in the surrounding medium. Analysis of the membrane proteins of the resistant S. epidermidis strain grown in the presence or absence of sub-inhibitory levels of teicoplanin (4 mg/L), showed the presence of a 39 kDa protein which was either absent, or present in considerably reduced amounts, in the sensitive strain. Fractionation of cell components after lysis of protoplasts showed that the 39 kDa protein was present predominantly in the membrane fraction but also in small amounts in the wall fraction. Similar investigations with S. haemolyticus revealed the presence of a 35 kDa protein in membranes of the resistant strain: the amount was increased substantially by growth in sub-inhibitory levels of teicoplanin. Membranes prepared by mechanical disintegration of bacteria or by osmotic lysis of protoplasts showed large apparent differences in the amounts of the 39 kDa protein.


A beta-lactamase-overproducing strain of Alcaligenes denitrificans subsp. xylosoxydans isolated from a case of meningitis.

A resistant (R) clinical isolate of Alcaligenes denitrificans subsp. xylosoxydans was recovered from CSF during treatment including piperacillin. This variant selected in vivo, and a second variant obtained in vitro from the initially susceptible (S) strain, both exhibited resistance to penicillins (ticarcillin, piperacillin) and cephalosporins, but remained susceptible to latamoxef and imipenem. Clavulanate (2 mg/L) restored the susceptibility of the two R-variants to penicillins. A beta-lactamase of pI 9.5 was detected in both S and R strains, but overproduction was observed only in the in-vivo and in-vitro R-variants. This inducible beta-lactamase hydrolysed benzylpenicillin, cephalothin and cephaloridine efficiently, but amoxycillin, ticarcillin and cefoperazone were only moderate substrates. The enzyme was inhibited by clavulanate, cloxacillin and imipenem (IC50 between 3 and 9 mM), but not by aztreonam and chloride ions (1 mM). Resistance to beta-lactams was not transferable by conjugation to Escherichia coli or Pseudomonas aeruginosa, and DNA agarose gel electrophoresis indicated that no plasmid was present in the isolates. Restriction patterns of chromosomal DNA isolated from the S and R isolates were similar after digestion by NotI and HindIII.


A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans.

6-Hydroxy-N-methyl-N-(2-[4-phenylphenyl] ethyl)-1,2,3,4-tetrahydro-1- napthalene methanamine (A60586), a new non-azole inhibitor of ergosterol biosynthesis in Candida albicans ATCC62376 has been identified. In whole cells A60586 produced a dose related reduction of [14C]acetate incorporation into ergosterol and a concurrent increase in the radiolabelling of 4,4-dimethylated sterols. Similar observations were made with [14C]mevalonic acid lactone labelled cell free extracts. The IC50s for inhibition of ergosterol in the whole cell and cell free systems were 22 microM (10 mg/L) and 7.8 microM (3.5 mg/L), respectively. Analysis by gas chromatography of sterols from cells previously incubated at 37 degrees C for 24 h with A60586 (200 mg/L) confirmed the presence of lanosterol and 14 alpha-methyl fecosterol. These data indicate that A60586, inhibits the demethylation of the C-14 methyl group of lanosterol. The MIC of A60586 for several candida strains ranged from 12.5 to 50 mg/L, and against Cryptococcus albidus and Aspergillus niger ranged from 50 to 100 mg/L. The best in-vitro activity of A60586 was against Torulopsis glabrata (MIC range = 3.12 to 50 mg/L). The membrane permeabilizing effect of this compound (50% leakage of [14C]aminoisobutyric acid at 70 mg/L A60586) may have contributed to its in-vitro antifungal activity.


Growth-rate-independent killing by ciprofloxacin of biofilm-derived Staphylococcus epidermidis; evidence for cell-cycle dependency.

Cell culture methods that allow culture of Staphylococcus epidermidis biofilms at controlled growth rates were used to examine susceptibility to ciprofloxacin. Changes in biofilm susceptibility, dependent upon growth rate, were compared with those for suspended populations grown in chemostat, and also for newly-formed daughter cells shed from the biofilm during its growth and development. Susceptibility increased for intact and resuspended biofilms, and also for planktonic cultures, with increases in growth rate. The dependence of susceptibility upon growth rate was greatest for slow growing cells (mu, 0.01-0.15/h). At any particular growth rate, biofilms appeared more susceptible than their planktonic counterparts. Newly-formed daughter cells were relatively tolerant to ciprofloxacin at all rates of growth. Lack of growth rate dependency for the newly-formed cells suggested a role for the cell-division cycle in determining resistance. This was confirmed by examining the susceptibility of S. epidermidis throughout batch cultures with cell division synchronized. Perfusion of various steady-state biofilms with ciprofloxacin demonstrated killing of the adherent population even at much reduced rates of growth.


Effect of biofilm culture upon the susceptibility of Staphylococcus epidermidis to tobramycin.

Biofilms of Staphylococcus epidermidis were cultured at various specific growth rates, and susceptibilities to tobramycin were compared with those of equivalent plank-tonic populations. In all instances, susceptibility increased significantly with increasing specific growth rate. However, resuspension of the biofilms increased susceptibility, suggesting some involvement of the glycocalyx in reducing antibiotic permeation of the biofilm. Cells that dispersed spontaneously from the biofilms at steady state were particularly susceptible to this agent. Since such cells correspond to newly-divided daughter cells, the relationship between tobramycin susceptibility and the phase in the division cycle was investigated. Susceptibility was enhanced in cultures dividing synchronously shortly before, during and shortly after cell separation. Perfusion of actively-growing S. epidermidis biofilms with tobramycin also demonstrated increased susceptibility with increasing growth rate, but also showed rapid recovery following removal of the agent.


Antimicrobial susceptibility of anaerobic bacteria in Australia.

The susceptibilities of 900 clinical isolates of anaerobic bacteria to 14 antimicrobial agents were determined by an agar dilution technique. Chloramphenicol, imipenem and metronidazole were found to be active against virtually all of the strains; only a single Bacteroides fragilis isolate was resistant to both imipenem and metronidazole. The addition of clavulanic acid to amoxycillin and ticarcillin potentiated the activities of these agents against all anaerobes including members of the B. fragilis group. Ampicillin/sulbactam and clindamycin were the next most active agents, 91 and 89% of isolates respectively being susceptible. Seventy-three per cent of the bacteria tested were susceptible to cefoxitin and 65% to cefotetan, with the MICs of almost 50% of the isolates clustering between 16 and 32 mg/L. There was also clustering around the breakpoint (64 mg/L) of piperacillin. Azithromycin exhibited poor activity against the B. fragilis group; only 18% of isolates were susceptible to < or = 4 mg/L. However, 92% of non-B. fragilis Bacteroides group strains were susceptible to this agent. We conclude that imipenem, metronidazole, chloramphenicol, ticarcillin/clavulanate, co-amoxiclav and, to a lesser extent, ampicillin/sulbactam are suitable as empirical therapy for infections caused by anaerobic bacteria.


Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.

The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.


The activity of hydroxynaphthoquinones against Leishmania donovani.

The hydroxynaphthoquinones, buparvaquone, 250C80 and 56W82, showed high activity in vitro against Leishmania donovani amastigotes in mouse peritoneal macrophages, with ED50 values of 0.05, 2.95 and 13.82 microM, respectively. Fourteen other hydroxynaphthoquinones were tested, of which only 566C80 and 608C86 showed significant activity against amastigotes. Buparvaquone, 250C80 and 56W82 were also highly-active against cultured promastigotes. In a BALB/c mouse model, treatment with 100 mg/kg/day for five days with buparvaquone, 250C80 and 566C80 (atovaquone) reduced liver amastigote numbers by 60%, 22% and 30.5%, respectively.


In-vivo activity of streptomycin and clofazimine against established infections of Mycobacterium avium complex in beige mice.

Beige mice were challenged with 10(6)-10(7) cfu of Mycobacterium avium intracellulare strain 101 and 22 days later treated with streptomycin 150 mg/kg/day alone, clofazimine 20 mg/kg/day alone, streptomycin 150 mg/kg/day plus clofazimine 20 mg/kg/day, or no antimicrobial agent (untreated controls). Both single-drug therapies partially reduced the cfu counts in spleen, liver and lungs compared with the controls however the combination was significantly more effective and completely eliminated the pathogen from the spleen and lungs of some animals after eight weeks treatment.


A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.


Cost-effectiveness of single dose cefotaxime plus metronidazole compared with three doses each of cefuroxime plus metronidazole for the prevention of wound infection after colorectal surgery.

The cost-effectiveness of prophylaxis for colonic surgery with single dose cefotaxime plus metronidazole has been compared with that of three doses each of cefuroxime plus metronidazole, by analysing data from a previously published study supplemented with additional data on the hospital and community costs of wound infection after colonic surgery. The original trial included 942 patients having elective colonic surgery in 14 hospitals. The data on costs of wound infection were collected from a further 124 patients undergoing elective colonic surgery at Ninewells Hospital. All these patients received a three dose regimen of cefuroxime plus metronidazole. The Dundee patients received three injections of 0.75 g cefuroxime at 8-hourly intervals whereas the trial patients received a single dose of 1.5 g followed by two further doses of 0.75 g at 8-hourly intervals. The cefuroxime prophylaxis regimen used in the trial cost 24.16 pounds per patient more than the cefotaxime regimen. The components of the excess cost were drugs (15.18 pounds), equipment (6.14 pounds) and staff time (2.84 pounds). The median cost to the hospital of a wound infection was 978.04 pounds (95% CI 482.04 pounds to 1521.22 pounds). The components of the hospital cost of wound infection were: hotel costs 858 pounds (88%), dressing costs 83.02 pounds (8%) and drug costs (excluding prophylaxis) 37.02 pounds (4%). Only five patients received additional antibiotic treatment in the community, and only one required home visits from the District Nurse. Applying the difference in costs of prophylaxis as 21 pounds (costs of drugs plus equipment) and the cost per wound infection as 1000 pounds to the observed wound infection rate of 7% in the cefuroxime group, the wound infection rate in the cefotaxime group would have to be 2.1% higher for the two regimens to be equally cost-effective. The probability that such a difference in efficacy exists is 0.088. A model was developed to calculate the probability of equal cost-effectiveness over a range of costs of wound infection.


Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function.

Some phosphodiesterase (PDE)-inhibitors are believed to alter platelet count and function due to changes in intracellular cAMP. Whether newly developed (specific) PDE-inhibitors negatively influence platelet function in cardiac surgery should be investigated in a randomized study. Eighty patients undergoing aorto-coronary bypass grafting were divided into 4 groups and received either the new PDE-III-inhibitor piroximone (group 1), the PDE-III-inhibitor enoximone (group 2), epinephrine (group 3) or no inotropic support (control). PDE-III-inhibitors were given as a bolus followed by infusion until starting of cardiopulmonary bypass (CPB). In addition to platelet count and a thrombelastogram, platelet function was assessed by aggregometry (ADP, epinephrine, collagen). Measurements were done before, during and after CPB until the 1st postoperative day. Platelet count and postoperative blood loss did not differ between the groups within the entire investigation period. Maximum aggregation and maximum gradient of platelet aggregation to all stimuli were not changed by either PDE-inhibitor enoximone or piroximone. CPB resulted in a significant decrease of all aggregation variables which was without differences due to treatment. Platelet aggregation recovered in the post-bypass period and exceeded baseline values on the 1st postoperative day. It is concluded that enoximone and the new PDE-III-inhibitor piroximone do not affect platelet function and can be used before CPB without risking platelet-related bleeding in cardiosurgical patients in the perioperative period.


Cerebral blood flow and cerebral oxygen consumption in patients with COPD on mechanical ventilation.

To investigate the effect of PaCO2 on cerebral blood flow (CBF) in chronic obstructive pulmonary disease (COPD). Before-after trial. General ICU in a regional hospital. 7 patients undergoing mechanical ventilation because of an exacerbation of COPD. CBF and cerebral metabolic rate of oxygen (CMRO2) of COPD were measured before and after hyperventilation and were compared by those of normal patients. CBF was measured by the Kety-Schmidt technique using 15% N2O. Hyperventilation produced a significant reduction in CBF in COPD with no concomitant change in CMRO2. CMRO2 in COPD was significantly lower than those in normal patients. The regression equation was shifted significantly more to the right in COPD. The sensitivity of CBF in CO2 remained but CMRO2 was reduced markedly in COPD patients.


The effect of selective decontamination of the digestive tract on gastrointestinal enterococcal colonization in ITU patients.

The effect of selective decontamination of the digestive tract (SDD) on Intensive Therapy Unit (ITU)-acquired enterococcal infection and colonization was studied. Changes in the predominant species isolated and resistance patterns to antimicrobial agents were also studied. Three groups were investigated: historical control (HC), contemporaneous control (CC) and patients receiving SDD (topical polymyxin, amphotericin B and tobramycin throughout ITU stay with intravenous ceftazidime for the first 3 days only). Adult general ITU with 7 beds. Patients with a nasogastric tube in situ and who were likely to remain in ITU for 48 h or longer were recruited. Enterococcal infections occurred in 3 of 84 HC patients and 2 of 91 CC patients. There were no unit-acquired enterococcal infections in the SDD group. There were 140 episodes of enterococcal colonization occurring in 112 patients, with significantly more in the SDD and CC groups (p < 0.05. There were no significant differences in antibiotic sensitivities between the three groups. Enterococcus faecalis was the most frequently isolated species. SDD does not predispose to enterococcal infection but does encourage colonization in patients receiving the regimen and other patients in ITU at the same. There is a complex interaction of factors which influence faecal flora and the likelihood of patients becoming colonized or infected with enterococci.


Electron-microscopic description of accretions occurring on tips of infected and non-infected central venous catheters.

The purpose of the study was do describe the architecture of accretions occurring on the tips of central venous catheters (CVC). A conservative procedure was used followed by two different techniques of electron microscopy. the study included 19 catheters which have been used on intensive cared adults, and which were chosen among those of parallel 300 CVC study. CVC were considered sterile, contaminated, colonized or infected according to microbiological and clinical criteria. CVC were found to remain much cleaner than in past descriptions. When present, accretions were located on the olive-shaped end, and displayed stratified structures with three types of material: amorphous material, thrombus components and inflammatory cells. Bacteria were not seen, even on culture positive CVC. Candida albicans was found on one CVC in the cytoplasm of granulocytes, and made no direct contact with the plastic surface. This technique should contribute to the understanding of the pathobiology of CVC infection and provide information proving or precluding the involvement of microbial adherence to polymers in vivo.


Possible risk for cardiac arrhythmia related to intravenous erythromycin.

To evaluate the incidence of prolongation of the rate-corrected electrocardiographic QT interval (QTc) and of ventricular arrhythmia associated with intravenous administration of erythromycin lactobionate. A consecutive series of 7 critically ill patients treated with intravenous erythromycin for severe pneumonia. A medical intensive care unit of a university hospital. Registration of QTc duration before and after intravenous administration of erythromycin as a short infusion. Blood chemistry, hemodynamic variables, arrhythmias, and co-medications were recorded. Evaluation of at least 10 ECG intervals by 2 experienced investigators who were blinded as to the time of drug administration. If several measurements were performed in the same patient, only the mean value was used for further analysis. During 12 of 13 drug administrations studied in 7 patients QTc prolongation was observed. The extent of QTc prolongation was significantly correlated with the infusion rate (mg/min, r = 0.765, p = 0.05). In 3 patients ventricular arrhythmia occurred in close temporal relation to the erythromycin infusion; two of them developed ventricular fibrillation shortly after the first and second dose of erythromycin, respectively, and died within 3 h. In critically ill patients erythromycin-induced QTc prolongation is a frequent pharmacologic effect correlated with erythromycin infusion rate. To avoid changes in electrocardiographic intervals and thereby possibly potentially life-threatening ventricular arrhythmia administration with the lowest possible infusion rate and close cardiac rhythm monitoring are advisable in these patients.


The influence of different levels of PEEP on peripheral tissue perfusion measured by subcutaneous and transcutaneous oxygen tension.

To compare subcutaneous (PscO2) and transcutaneous (PtcO2) oxygen tension measurements in relation to hemodynamic variables at different levels of PEEP, and to evaluate the usefulness of these measurements as monitors of peripheral tissue perfusion. Prospective trial. Intensive care unit in a university hospital. Seven patients with gastric cancer who where undergoing total gastrectomy. Silicone catheter was placed in the upper arm and transcutaneous oxygen monitor was placed on the upper part of the chest. A pulmonary artery catheter was placed in the right pulmonary artery. PscO2 and PtcO2 together with hemodynamic variables were measured at different levels of PEEP. Progressive increase of PEEP reduced cardiac index (CI) (p < 0.05) with a concomitant decrease of PscO2 (p < 0.05) and oxygen delivery (DO2) (p < 0.05). Changes in PtcO2 paralleled changes in arterial oxygen tension (PaO2), but no correlation was found between PtcO2, CI and DO2. PscO2 is a sensitive indicator of subcutaneous tissue perfusion, which can be used to identify the PEEP level, with optimum peripheral perfusion. PscO2 seems to be a more reliable indicator of tissue perfusion than PtcO2.


Differential lung ventilation with a double-lumen tracheostomy tube in unilateral refractory atelectasis.

Two patients with refractory hypoxemia due to unilateral lung atelectasis were treated with differential lung ventilation (DLV) through a Robertshaw-type, double-lumen tracheostomy tube. DLV was applied using two non-synchronized ventilators and maintained for 6 and 3 days, respectively. Ventilator settings were chosen in accord to the clinical, laboratory and chest X-rays results. Particularly, tidal volume and PEEP were set to avoid excessively high alveolar pressure and to obtain the highest possible value of compliance. We investigated the mechanical properties of the two lungs separately by measuring airway pressure and compliance of each lung before the beginning of DLV and at 0, 5, 24, and 48 h after. Initially we observed in both patients very low values of compliance (7-9 cm H2O/l) and a significant level of PEEPi (12-8 cm H2O) of the diseased lung, whereas PEEPi in the healthy lung was negligible. The clinical improvement was assessed by sequential chest X-rays and by significant improvement of arterial blood gas and PaO2/FiO2 ratios and was associated with a progressive increase of compliance (24-22 cm H2O/l) and by a fall of PEEPi levels (5-4 cm H2O) of the diseased lung. We also observed an improvement of SvO2, O2AVI, PVRI and Qva/Qt values (Case 1). The tracheostomy tube used to apply DLV was very reliable, allowing easy nursing care and selective bronchial aspirations. We conclude that DLV is a very useful technique in unilateral lung pathology, and it can be a life saving procedure in selected patients, by supplying volume and PEEP more efficiently to the affected lung.


Failure of thiamphenicol in a penicillin-allergic patient with Listeria meningoencephalitis--delayed cure following penicillin desensitization.

A 27-year-old woman, without compromised immunodefenses, experienced a Listeria meningoencephalitis, with brainstem symptoms. The identified agent exhibited poor susceptibility to usual effective antibiotics, except for penicillins. Knowledge of past history of an allergic reaction to beta-lactam antibiotics lead to appropriate therapy after acute intravenous desensitization of the patient to amoxicillin. Treatment resulted in therapeutic administration rate over 24 h, and in rapid regression of clinical and biological disorders.


Clostridial sepsis with massive intravascular hemolysis: rapid diagnosis and successful treatment.

A 61-year-old man developed a pyrescia accompanied by a massive intravascular hemolysis after abdominal surgery (Whipple's operation) of a pancreatic adenocarcinoma. Abdominal ultrasound and the abdominal CT-scan showed marked aerobilia and multiple liver abscesses. Laboratory tests demonstrated the presence of the Thomsen-Friedenreich cryptantigen (TCA) on the membranes of the patient's erythrocytes. The enzymatic cleavage of N-acetyl-neuraminic acid usually covering the TCA may lead to a life threatening intravascular hemolysis. Since Clostridial bacteriae typically synthesize neuraminidase, the presumptive diagnosis of Clostridial sepsis complicated by massive hemolysis was made. Immediate antibiotic therapy including penicillin G and metronidazole stopped hemolysis within a few hours and the patient servived. On the following day, microbiological examination identified Clostridium perfringens in the patient's blood cultures. Clostrial sepsis should be suspected in patients with underlying infections and/or malignant diseases, particularly of the gastrointestinal or genitourinary tract, who present with septic shock and acute intravascular hemolysis. Whereas microbiological specification of the organism is time consuming, the relatively simple agglutination test with anti-TCA peanut lectin can provide a rapid presumptive diagnosis. The immediate onset of an appropriate antimicrobial therapy is of central importance and might be life-saving.


Rare procedures during delivery room resuscitation--cardioversion of ventricular tachycardia in an asphyctic neonate.

Successful cardioversion of ventricular tachycardia in a full-term male infant, born severely depressed by emergency Cesarean section 9 min after the mother was given bilateral paracervical bupivacaine blocks for pain relief during normal labor, is described. The apparently stillborn baby was resuscitated by conventional means until electronic heart monitoring revealed transition from asystole to rapid ventricular tachycardia 14 min after birth. At 20 min, cardioversion with 5 watt-second was performed with successful reversion to sinus rhythm. The child recovered rapidly and neurological status at 12 months was normal. Obviously, active search and aggressive management of rapid ventricular arrhythmias are indicated during neonatal resuscitation, if potentially arrhythmogenic drugs are used in perinatal care.


Hemodynamic responses to noxious stimuli in brain-dead organ donors.

The case report presents evidence for the spinal origin of the marked hypertensive responses to noxious stimuli that may occur in organ donors who fulfill the commonly accepted criteria of brain death. Cardiovascular spinal reflex activity does not invalidate these criteria. For the first time, the catecholamine plasma concentrations have been determined during spinal pressor reflex activity. Circulating epinephrine increased more markedly than norepinephrine in both cases, rising to 4.7 and 44 times the baseline concentration respectively. The relation between plasma norepinephrine and epinephrine suggests involvement of the adrenal medulla in the reflex arc. The literature on spinal hemodynamic reflexes is reviewed.


The trigemino-pupillary reflex: a model of sensory-vegetative integration.

Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms.


Hypogastric nerve section reveals a role for both afferent and efferent fibres in the feline continence process.

The role of the hypogastric afferent and efferent innervation in the process of urine storage during natural rate filling was examined in the pentobarbitone anaesthetized cat. The observed changes in bladder pressure following hypogastric nerve section demonstrated the presence of baseline sympatho-inhibitory and phasic sympatho-excitatory influences for a significant portion of each distension, which proceeded to a volume just over halfway through the continence process. A reduction in bladder wall compliance at the end of the distensions provided evidence for a net sympatho-inhibitory influence in the second half of the continence phase. Hypogastric nerve section also resulted in a reduction in the reflex increase in hypogastric efferent nerve activity, measured in-continuity. This suggested that hypogastric afferent fibres made a significant contribution to the regulation of sympathetic hypogastric nerve activity during natural rate filling.


Alteration in sympathetic nerve activity during liver regeneration in rats after partial hepatectomy.

To determine if the sympathetic nerve has a role in liver regeneration, the alterations of tissue norepinephrine (NE) content and its turnover were measured in rats after partial hepatectomy. NE content per unit liver mass decreased progressively to about one-fourth of controls by the ninth day after partial hepatectomy. Since the total amount of NE in the whole liver did not change during nine days of liver regeneration, it was supposed that sympathetic innervation could make slower progress than proliferation of hepatocytes. Fractional turnover rate of NE was reduced transiently in regenerating liver 24-48 h after partial hepatectomy and recovered to normal 8-9 days after the operation. Such a transient reduction of NE turnover was observed specifically in the liver. These results suggest that sympathetic nerve activity of the liver is suppressed at the early stage of regeneration.


Normal sympathetic nerve activity in a reflex sympathetic dystrophy with marked skin vasoconstriction.

Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old patient with reflex sympathetic dystrophy (allodynia, marked vasoconstriction in the ulnar part of the left hand) following Vth finger amputation. Skin sympathetic activity showed normal characteristics with a weak discharge at rest whereas bursts of impulses could be evoked by sympatho-excitatory stimuli. Sympathetic bursts induced by painful stimuli were few, also during long-lasting allodynic pain. Sympathetic bursts induced by inspiratory gasps were not associated with excacerbation of pain. The discrepancy between the marked skin vasoconstriction and the low resting sympathetic discharge underlines the fact that sympathetic effector organ hyperactivity (i.e. vasoconstriction and/or hyperhidrosis) cannot be taken as evidence for increased sympathetic discharge. In the present case, the neuropathic pain syndrome cannot be considered as maintained by an increased sympathetic neural discharge to the symptomatic limb.


Vagal stimulation and cardiac chronotropy in rats.

Increasing frequencies of electrical stimulation of the right vagus nerve in the rat yielded a progressive lengthening of heart periods. Stimulation was capable of driving vagal control of cardiac chronotropy over its full physiological dynamic range, to the point of sinus block. The steady-state transfer function between vagal stimulation frequency and cardiac chronotropy was approximately linear, with a slope of 7.4 ms/Hz. The linearity of the stimulation-heart period function is consistent with previous reports in dogs, rabbits and humans, although the slope of the function was considerably lower in the rat.


Cortisol effect on atrial natriuretic factor response to hypertonic saline in fetal sheep.

Atrial natriuretic factor (ANF) is released following a variety of stimuli including hypertonicity in the fetus. To study the effect that cortisol has on fetal ANF release, seven chronically instrumented fetal sheep at gestational ages ranging from 110-132 days were studied in two experiments. In one experiment (CORTISOL), a continuous cortisol (with EtOH vehicle) infusion was maintained. In the other experiment (CONTROL), the vehicle was infused alone. Ninety minutes from the start of this infusion, a hypertonic saline bolus (12 meg/kg) was given. Osmolality, ANF, cortisol, pH, PO2, PCO2, mean arterial pressure (MAP), heart rate (HR), and hematocrit (HCT) were followed over a 120-min period. Following hypertonic saline, serum osmolality increased from 290.6 +/- 2.3 mOsm/kg to 310.4 +/- 2.5 mOsm/kg (P < 0.01). Baseline values for pH, PO2, and HCT were 7.37 +/- 0.01, 22.5 +/- 1.6 mmHg, and 33.9 +/- 1.2 respectively. Each of these variables fell following hypertonic saline infusion. MAP rose from 40.6 +/- 1.7 mmHg to 47.0 +/- 2.4 mmHg (P < 0.01). However, there were no differences between CONTROL and CORTISOL experiments in any of the above changes. Cortisol levels in the CONTROL group did not change during the course of the experiment, but in the CORTISOL group rose from 8.2 +/- 4.4 ng/ml to 33.0 +/- 9.9 ng/ml (P = 0.02). Plasma ANF levels prior to hypertonic saline were similar (124.8 +/- 17.7 pg/ml and 127.6 +/- 26.1 pg/ml) in the CONTROL and CORTISOL groups respectively and rose following hypertonic saline to a maximum of 155.3 +/- 16.6 pg/ml and 189.2 +/- 42.7 pg/ml (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of indomethacin on fetal renal function, renal and umbilicoplacental blood flow and lung liquid production.

The effects of indomethacin (10 mg/kg i.v. to the ewe and 12 mg/kg i.v. to the fetus) were examined in 8 chronically catheterized fetal sheep (117-138 days gestation). These doses suppressed fetal 6-keto-prostaglandin F1 alpha and thromboxane B2 levels. Fetal arterial PO2 increased (P < 0.01); PCO2 (P < 0.001) and pH fell (P < 0.001) and arterial pressure did not change. Placental blood flow increased in 4 of the 5 fetuses in which blood flows were measured. Lung liquid flow rate fell (P < 0.001). Fetal renal blood flow did not change but its distribution did, i.e. flow to the inner part of the renal cortex decreased (P < 0.05). Urine flow rates did not change but there was a natriuresis (P < 0.02), kaliuresis (P < 0.02) and chloriuresis (P < 0.02). Urinary osmolality rose (P < 0.001) and free water clearance fell (P = 0.004). It is concluded that when indomethacin is administered to both ewe and fetus, the resulting fall in prostaglandin I2 and thromboxane A2 levels causes marked changes in fetal blood gas status, renal function and lung liquid production. These effects are more profound than those seen when indomethacin is given only to the fetus. They do not however, explain the reason why clinical use of indomethacin is associated with a reversible oligohydramnios.


Repeated maternal separation in the neonatal rat: cellular mechanisms contributing to brain growth sparing.

Separation of neonates from their dam has been shown to evoke acutely a variety of biochemical responses, typified by depression of ornithine decarboxylase (ODC) activity. In the current study where rat pups were removed from their nursing dams for 6 h, ODC activities in the liver, heart, kidney and lung were markedly suppressed, but the enzyme in the brain was not altered during the early postnatal ages. These data suggest that the brain was protected from maternal separation insults, a homeostatic response mediated in part, by an increase of circulating corticosterone and glycogen mobilization from peripheral tissues, particularly the liver. In addition, we examined whether these responses were extended to pups who were subject to repeated episodes of maternal deprivation, and whether this stress paradigm might be associated with corresponding changes of cellular growth and maturation. Pups were removed from their dams for 6 h daily beginning at 4 days of age until weaning at 21 days. Plasma corticosterone levels of the deprived pups were elevated significantly at the end of each stress episode but returned to basal (control) levels subsequently. The repeating stress paradigm did not influence the magnitude of this hormonal response at the ensuing ages. Consistent with findings observed in the single episodes of stress, ODC activities in the peripheral tissues were significantly depressed in pups subject to repeated maternal deprivation, but the enzyme appeared to recover to control levels 18 h after each insult. In contrast, brain ODC activity did not exhibit any change throughout the period examined. Moreover, while ontogenetic gains of DNA and protein in the peripheral tissues of the deprived rats lagged slightly but consistently behind those of controls, these macromolecules in the brain were not affected appreciably. These results thus suggest that brain growth was, by and large, spared from insults associated with repeated maternal separation; but this stressful paradigm did produce marked, though reversible biochemical and physiological responses in the peripheral tissues of neonates, which cumulatively led to a lag of cellular development.


Amniotic fluid and plasma glycine/valine ratios in substrate deprived growth retarded fetal rats.

Characteristic profiles of the free amino acid concentration in umbilical cord blood of growth retarded newborns have been observed. We hypothesized that the amniotic fluid of growth retarded fetal rats would show an increase in the ratio between glycine and valine which would parallel the pattern observed in the cord blood of growth retarded neonates, thus providing an index for the antepartum identification of the substrate deprived growth retarded fetus. Six test and 6 control dams were tested. Four fetuses per dam, matched for uterine location were examined. Test animals were fasted for 72 hours. Sampling was performed on day 21 under anaesthesia. Fetal size was significantly reduced (P < 0.0001) in the test group. [T = 2.68 gs. +/- 0.28 vs. C = 3.67 gs. +/- 0.25]. Fetal plasma concentrations of glycine showed an increase in test animals (P < 0.01) while valine showed a significant reduction (P < 0.0001). Glycine (pm/microliters) T = 308 +/- 64 vs. C = 269 +/- 47, valine (pm/microliters) T = 424 +/- 79 vs. C = 671 +/- 218]. Amniotic fluid concentrations for both glycine and valine were significantly decreased (P < 0.0001) in test animals. [Glycine (pm/microliters) T = 710 +/- 124 vs. C = 931 +/- 178; valine (pm/microliters) T = 845 +/- 169 vs. C = 1,339 +/- 234]. The glycine/valine ratio was significantly increased (P < 0.01) in both fetal plasma and amniotic fluid in test animals [Plasma T = 0.74 +/- 0.18 vs. C = 0.43 +/- 0.13. Amniotic fluid T = 0.85 +/- 0.08 vs. C = 0.69 +/- 0.09]. Consistent with our hypothesis, the amniotic fluid concentrations generally parallel the observations made in the plasma. This finding could enhance the antepartum identification of the substrate deprived growth retarded fetus.


Islet transplantation in diabetic pregnant rats normalizes glucose homeostasis in their offspring.

Diabetes of the mother during pregnancy induces alterations in the fetus, resulting in impaired glucose homeostasis in the offspring. In youngsters of severely diabetic mothers, during glucose infusion, hyperinsulinemia is associated with hyperresponsiveness of the beta-cells and insulin resistance. In order to normalize maternal metabolism, isolated islets from neonatal rats were transplanted into the vena porta of severely hyperglycemic (Streptozotocin) rats at day 15 of gestation. Strict glycemic control of the mothers was achieved throughout further gestation and lactation. In the adult offspring of these transplanted rats insulin levels during glucose infusion were significantly lower than in the offspring of sham-transplanted diabetic mothers and were not different from controls. The work confirms that the diabetic state of the mother during late gestation (the period of development of the endocrine pancreas and of the insulin-receptor system) is the inducing factor for the abnormal glucose homeostasis in the offspring, and normalisation of the hyperglycemia eliminates these long-term consequences.


The effect of hyperglycemia on acid-base and sympathoadrenal responses in the hypoxemic fetal monkey.

We investigated the influence of hyperglycemia on the fetal acid-base and sympathoadrenal responses to hypoxemia (maternal FIO2 9%) in rhesus monkey fetuses. In chronic preparations, we determined PO2, O2 content, PCO2, pH, lactate, glucose, insulin, catecholamines, heart rate, and arterial pressure. Combined hyperglycemia and hypoxemia resulted in a decrease in fetal pH and an increase in lactate; however, the magnitude of these changes was only modestly, and not significantly, greater than those observed during euglycemic hypoxemia. These effects were much less striking than expected, based on earlier work in sheep (Shelley, Bassett & Milner, 1975; Robillard, Sessions, Kennedy & Smith, 1978). Although catecholamines increased significantly in response to hypoxemia both in hyperglycemic and euglycemic fetuses, the increase was less in the hyperglycemic group, possibly resulting from a modulating effect of the high glucose concentration on catecholamine release from the adrenal medulla. Finally, a significant fetal insulin response to hyperglycemia was seen which, suggestively, was partially inhibited in the presence of hypoxemia and its associated increase in sympathoadrenal activity.


Vancomycin-resistant Enterococcus faecium in hospitalized children.

Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. Survey; case-control study. Children's hospital. Pediatric oncology patients. Contact isolation, restriction of vancomycin prescribing. There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.


Methicillin-resistant Staphylococcus aureus: a questionnaire survey of 75 long-term care facilities in western New York.

To determine the frequency of recognition of methicillin-resistant Staphylococcus aureus (MRSA) as an infection control problem and its prevalence among long-term care facilities, and to evaluate whether certain long-term care facility characteristics such as bed size, ownership, level of infection control activity, and frequency of resident transfers to acute care hospitals are related to the recognition or prevalence of MRSA in this setting. Questionnaire survey. Seventy-five long-term care facilities in the 8 counties of western New York. Seventy-five of 81 (92.6%) long-term care facilities returned a completed questionnaire. Seventy-nine percent were considered to have a "limited" level of infection control activity (part-time infection control practitioner who spent less than 10 hours a week on infection control activities). The larger the long-term care facility, the more time was spent on infection control activities (p = .01). Seventy-two percent of the long-term care facilities screened new admissions for MRSA by reviewing culture reports; 69% of the long-term care facilities had a specific infection control policy for MRSA. Sixteen of the 75 (21%) facilities felt they had an infection control problem with MRSA. By univariate analysis, the only characteristic significantly associated with this recognition was use of nurse practitioners or physician assistants by a facility (p < .05). Eighty-one percent of the 75 long-term care facilities had identified one or more patients with MRSA in the year prior to the survey. By univariate analysis, the only characteristics that were significantly associated with the number of residents with MRSA were the monthly average number of residents transferred to acute care facilities (p = .034) and facility bed size (p = .022); there was also a trend toward increasing intensity of infection control activities (p = .085). However, facility bed size and the average number of resident transfers per month to acute care facilities were strongly associated (p = .0002). By stepwise logistic regression analysis, only bed size was an independent predictor of the number of residents with MRSA. Many long-term care facilities had tried to eradicate MRSA; ciprofloxacin was most commonly used to eradicate MRSA. The vast majority of the 75 long-term care facilities in the 8 counties of western New York have identified patients with MRSA, although only a minority (21%) of them actually believed that an infection control problem existed. Facility size (a surrogate for the monthly average number of resident transfers to acute care facilities) seems to be an important factor in determining the number of residents with MRSA in long-term care facilities in our geographic region. The major longitudinal studies of MRSA in such facilities have so far been done only in Veterans Affairs facilities. Further studies are needed in freestanding long-term care facilities, the largest group of long-term care facilities in the United States, to determine the epidemiology of MRSA in this setting and to develop practical and valid infection control methods for residents with MRSA.


Healthcare workers' risk of contact with body fluids in a hospital: the effect of complying with the universal precautions policy.

To test whether healthcare workers' knowledge of and compliance with the basic principle of the Universal Precautions policy (i.e., that all patients should be treated equally regarding contact with body fluids) influenced the rate of contact with patient blood. Survey based on anonymous questionnaires. A 380-bed secondary and tertiary care hospital receiving emergency and elective patients. All employees having any contact with patients. Nine hundred one of 1,308 (69%) of the questionnaires were returned. Twelve percent of the respondents (95% confidence interval [CI95] = 10.0%-14.4%) had experienced any contact with patient blood in the week preceding their answer. Physicians had the highest rate of contact with blood followed by nurses. In the five groups--physicians, nurses, laboratory technicians and phlebotomists, nursing aides, and student nurses--contact with blood was less frequent in the subgroup that did know and comply with the basic principle of the Universal Precautions policy, compared with the subgroup that did not. When adding the results for the 5 groups, contact with blood was experienced by 91 of 571 (15.9%, CI95 = 13%-19%) of the personnel who did not know and comply with Universal Precautions. The personnel who did know and comply with Universal Precautions had a significantly lower (9 of 111 [8.1%], p < .05, CI95 = 3.8%-15%) rate of contact with blood. The healthcare workers who knew and complied with Universal Precautions had a significant lower rate of contact with patient blood than those who did not.


The ultrastructure of the noninvolved urothelium of tumor-bearing patients before and after interferon treatment.

The ultrastructural morphology of the noninvolved urothelium of tumor-bearing patients before and after interferon-alpha 2b (IFN-alpha 2b) treatment was investigated. The ultrastructure of the normal bladder urothelium has been reported. The noninvolved urothelium of our patients already showed deviation from the normal. At the end of therapy, we noted a partial restoration of the urothelium to its normal morphology with the reestablishment of some of its normal features, i.e., a well-developed Golgi apparatus, the existence of parts of the asymmetric unit membrane, and the appearance of nuclear bodies. Prevention of tumor recurrence by restoring the ultrastructural morphology of the noninvolved urothelium with IFN-alpha 2b is a subject worthy of further investigation.


Interferon-alpha/beta, pentoxifylline, and caffeine synergize with interferon-gamma to induce major histocompatibility complex class I expression on a constitutively class I-negative murine tumor cell line.

The constitutively class I-negative tumor cell line, Kgv, expresses H-2Dk in response to interferon-gamma (IFN-gamma), but not in response to IFN-alpha/beta, tumor necrosis factor, or lymphotoxin. H-2Dk expression was not induced on Kgv cells by the methylxanthines, pentoxifylline (PTX) and caffeine, which modulate class I expression on cells that constitutively express class I molecules. Treatment of Kgv cells with either IFN-alpha/beta, PTX, caffeine, or dibutyryl cAMP and a concentration of IFN-gamma insufficient by itself to induce Dk expression resulted in the induction of Dk expression. Since PTX and caffeine are cAMP-specific phosphodiesterase inhibitors, it is possible that the effects of PTX, caffeine, and dibutyryl cAMP involve a cAMP-dependent mechanism. We conclude that concentrations of IFN-gamma insufficient to induce Dk expression on Kgv cells may be capable of rendering the Dk gene responsive to signals that, in the absence of IFN-gamma treatment, have no effect on Dk expression.


Absence of biological effects of orally administered interferon-beta ser.

To assess biological effectiveness of interferon (IFN) administered orally, we measured serum IFN and several proteins and metabolites induced by IFN after oral administration of 2.5 mg or 7.5 mg of recombinant IFN-beta ser to 6 healthy volunteers. These IFN-induced metabolites, beta 2-microglobulin, and neopterin in serum, and 2',5'-oligoadenylate (2-5A) synthetase in peripheral blood mononuclear cells, are more sensitive to the presence of IFN than bioassay of IFN in serum. Up to 48 h after oral IFN was administered, serum IFN, beta 2-microglobulin, neopterin, or 2-5A synthetase were not generally increased compared to pretreatment levels, indicating that oral IFN had no significant biological effects.


"Discordant" influence of equine recombinant interferon-beta 1 on the cytotoxic capacity of equine polymorphonuclear neutrophils and peripheral blood mononuclear cells in vitro and in vivo.

The influence of recombinant equine interferon-beta 1 (rEqIFN-beta 1) on mononuclear cells of peripheral blood (PBMC) and polymorphonuclear neutrophilic granulocytes (PMN) was tested under in vitro and ex vivo conditions. Treatment of equine PBMC with IFN in vitro enhanced the antibody-independent cytotoxicity (AICC) and antibody-dependent cytotoxicity (ADCC) while there was no significant effect on the cytotoxic capacity of PMN treated with rEqIFN-beta 1 in vitro. Ex vivo there was an increased capacity of AICC and ADCC upon single or multiple application of rEqIFN-beta 1 in PMN, only. Treatment with rEqIFN-beta 1 thus induced an increased cellular cytotoxicity in vitro and in vivo but in different populations of peripheral blood cells. In vivo rEqIFN-beta 1 causes a pronounced activation of PMN but not of PBMC as cytotoxic effector cells. This might be achieved indirectly, e.g., by cytokines produced by IFN-sensitive cells.


Identification of a new interferon-alpha/beta-inducible DNA-binding protein that interacts with the regulatory element A of 2',5'-oligoadenylate synthetase ME-12 gene.

A new interferon (IFN)-stimulated response factor (ISRF) has been identified in nuclear extracts of IFN-alpha/beta-treated murine BALB/c-3T3 fibroblasts by the mobility-shift electrophoresis assay. The factor, ISRF-2, displays murine 2',5'-oligoadenylate (2-5A) synthetase ME-12 gene 5' regulatory element A specificity and differs from the previously described IFN response element B-specific factor ISRF-1 in several aspects. ISRF-2 is restricted to the nucleus, whereas ISRF-1 exists in the cytoplasm and translocates into the nucleus upon treatment of cells with IFN-alpha/beta. The ionic strength requirement of ISRF-2 for maximal DNA-binding activity is lower than that of ISRF-1. The DNA-binding activity of ISRF-2, but not that of ISRF-1, is markedly suppressed by Mg2+. In common with ISRF-1, the phosphorylated form of ISRF-2 appears to be required for DNA-binding activity. A model is proposed for the mechanism whereby murine IFN-alpha/beta regulates 2-5A synthetase ME-12 gene expression.


Acid lability is not an intrinsic property of interferon-alpha induced by HIV-infected cells.

Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon-alpha (al-IFN-alpha) in cultures of mononuclear cells from peripheral human blood. We have investigated the physiochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN-alpha is a mixture of both glycosylated and unglycosylated molecules as shown by separation on Concanavalin-A Sepharose. Acid-lability is associated only with glycosylated molecules. Upon chromatography of the glycosylated fraction on Sepharose coupled to IFN-alpha-specific antibody, the portion of the IFN that is retained and eluted with guanidine-HCl is acid-stable, whereas the excluded antiviral activity is acid-labile, and is partially neutralized by antibodies to either IFN-alpha or IFN-gamma. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-alpha. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-alpha column potentiates antiviral activity of the IFN that is specifically retained by the column. This potentiation is abolished by acid treatment. Similar results are obtained with al-IFN-alpha from the serum of acquired immunodeficiency syndrome (AIDS) patients, indicating that its acid-lability is also the consequence of an acid-labile component that is capable of enhancing the antiviral activity. The potentiation of antiviral activity obtained by combining recombinant preparations of IFN-alpha and IFN-gamma suggests that the cooperating molecule is IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)


Double-stranded RNA and interferon-alpha induce transcription through different molecular mechanisms.

Double-stranded (ds) RNA stimulates the synthesis of several mRNAs known to be induced by type I interferons (IFNs). In this report, it is shown that the IFN-alpha stimulated genes (ISGs) 15, 54, 56, and GBP are transcriptionally induced by dsRNA. Transcriptional stimulation occurred in the presence of the protein synthesis inhibitor cycloheximide (CHX), indicating that inducibility was directly mediated by dsRNA through the action of preformed proteins. ISGF-3, the protein complex mediating primary transcriptional induction of ISGs by IFN-alpha, was not activated by dsRNA in the presence of CHX. Additionally, DNA-binding activity of ISGF-2/IRF-1, a protein involved in the regulation of the IFN-beta gene and ISGs, did not correlate with dsRNA-induced transcriptional induction of ISGs. This suggests that dsRNA and IFN-alpha induce ISGs through different molecular mechanisms.


Phase II trials of interferons-alpha and -beta in advanced sarcomas.

Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies.


Oxidative stress. An early phenomenon characteristic of acute experimental pancreatitis.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were sacrificed at 1, 3, 6, and 24 h. Malondialdehyde and sulfhydryl groups concentration, as well as superoxide dismutase and catalase activity were measured in pancreatic, liver, and lung tissue. These parameters, with the exception of catalase, were also determined in serum and peritoneal exudate. Early and profound oxidative stress in each organ was evidenced by marked increases in malondialdehyde concentrations along with marked reductions in levels of sulfhydryl groups and superoxide dismutase; a paradoxical increase in catalase activity, perhaps compensatory, was noted in pancreas and lung. Survival for 24 h was associated with restoration of normality insofar as tissue malondialdehyde concentrations were concerned, but pancreas sulfhydryl groups remained markedly depleted. These data endorse the suggestion that the early provision of such compounds may help to accelerate recovery from hemorrhagic pancreatitis in humans.


Intraoperative endoscopic electrohydraulic lithotripsy of pancreatic stones.

Two male patients with complications associated with chronic pancreatitis are described. In each patient, preoperative examinations revealed a large stone obstructing the main duct in the head of the pancreas. Lateral pancreaticojejunostomy was performed to relieve pain and prevent further attacks of pancreatitis. During each operation, the stone was fragmented under direct visual control with the use of a flexible choledochoscope and a contact electrohydraulic lithotriptor. The stone was removed and ductal flow through the head of the pancreas was reestablished. Our experience shows that endoscopic electrohydraulic lithotripsy facilitates operative removal of pancreatic stones deeply located in the head of the pancreas.


Intraoperative ultrasonography in surgery for chronic pancreatitis.

We report our experience with intraoperative ultrasonography in 49 patients undergoing surgery for chronic pancreatitis. Among drainage procedures, there were 14 laterolateral pancreaticojejunostomies, 15 pseudocystojejunostomies, and 2 pseudocystoduodenostomies. Under the guidance of intraoperative ultrasonography, left sided partial resection of the pancreas was performed in 7 patients, whereas a Whipple-type procedure was necessary in 6 cases. All preoperatively diagnosed pseudocysts, abscess formations, and dilated pancreatic ductal systems could be easily localized with the assistance of intraoperative ultrasound. Additionally to diagnoses already made preoperatively, intraoperative ultrasonography revealed a second, smaller pseudocyst in one patient and pancreaticolithiasis in another case. However, significant assistance and comfort to the operating surgeon was provided in all cases by intraoperative ultrasound imaging. This technique, which is cost effective and minimally invasive, proved to be extremely helpful in localizing pancreatic fluid collections and the course of the pancreatic duct. It facilitates the operation by reducing tissue traumatization and operative time. In experienced hands, intraoperative ultrasonography is a reliable method and a useful adjunct to the surgeon.


Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study.

This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5-fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing.


Human amniotic fluid obtained from diabetic women. A potent stimulator of islet cell replication.

Recently, human amniotic fluid (HAF) from healthy women was found to stimulate growth and function of pancreatic B-cells. Here, the effect of HAF and serum from healthy probands (HS) was compared with that from probands with gestational (GD), noninsulin-dependent (NIDDM), or insulin-dependent diabetes (IDDM) on islet function and replication. Rat islets were cultured in the presence of either HAF or HS for 7 d. Insulin content and basal insulin release were not different after exposure of the islets to HAF or HS from healthy or diabetic women. In contrast to HS, HAF provoked the islets to deliver significantly more insulin during culture. Additionally, the same islets exhibited a more intense response to a glucose challenge. The degree of HAF-induced insulin release was not influenced by the type of diabetes. HAF and HS from GD and NIDDM women did not influence the islet DNA synthesis in comparison to HAF and HS from healthy pregnant women. However, HAF but not HS from IDDM pregnant women, elicited a significant increase in islet replication. Most effective in stimulating islet cell replication were HAFs from IDDM pregnant women belonging to the White D-type. It was shown that the relatively high concentration of insulin in the HAFs was not directly responsible for the observed increase of the islet DNA synthesis. HAF from women with long-term diabetes is supposed to contain factor(s) that might directly or indirectly enhance islet replication.


Determination of pancreatic lipase by immunoactivation technology. A rapid test system with high sensitivity and specificity.

This paper describes the test characteristics and clinical relevance of a newly developed homogeneous enzyme immunoassay IMAC lipase test for the determination of serum pancreatic lipase. The method of determination is based on an immunoactivation technology and utilizes antibody fragments against human pancreatic lipase covalently bound to the marker enzyme horseradish peroxidase. The serum samples of 408 persons were investigated with this new assay. The within-run and day-to-day precision, the linearity, and the recovery of this immunoassay correspond to a very high degree to the requirements made of a modern immunological test. Comparison with an ELISA method resulted in a correlation coefficient of 0.971, whereby the IMAC lipase assay tended to register lower serum values. The serum range for the IMAC lipase test is 0-47 micrograms/L, based on a normal collective of 187 healthy controls. A sensitivity of 95.8% for the diagnosis of acute pancreatitis at a cutoff level of twice the upper normal range and a specificity of 99.3% at an efficiency of 99.8% can be given. The advantage of the IMAC lipase test method is its ability to be adapted to work on automatic laboratory analyzers.


Expression of the human MUC1 mucin cDNA in a hamster pancreatic tumor cell line HP-1.

A full length cDNA for the human mucin gene, MUC1, under the control of human beta actin promoter, was transfected into a carcinogen induced hamster pancreatic ductal tumor cell line, HP-1. Transfectants were selected by resistance to geneticin. Integration of the foreign human MUC1 cDNA occurred at multiple sites in the genome of HP-1. Northern blot analysis showed MUC1 expression in cells transfected with MUC1 cDNA placed in the correct orientation, but not in control cells (HP-1 cells transfected with vector alone, or with the MUC1 cDNA placed in the antisense orientation). Western blot analysis using monoclonal antibody HMFG-2, which is reactive with the MUC1 protein, showed results consistent with the Northern blot data. Positive immunoperoxidase staining using HMFG-2 was seen in HP-1 cells transfected with MUC1 cDNA but not with untransfected or HP-1 control cells. The integration of human MUC1 mucin gene in HP-1 cells caused no significant change in the growth rate of HP-1 cells in vitro, but resulted in an enhanced growth rate for xenografts of MUC1 transfected HP-1 cells grown in nude mice.


Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.


Pancreatic carcinoma associated with chronic calcifying pancreatitis.

A total of 160 Japanese patients with pancreatic carcinoma were treated in the Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan, from January 1976 to December 1991. Four of these patients had an accompanying pancreatic calcification with a 2.5% incidence of pancreatic carcinoma. Those four patients consisted of 52, 75, 75, and 82 year-old men. Three complained of jaundice and another developed an abdominal mass. Two of the four patients were diabetic and had a past history of heavy alcoholic intake. Three pancreatic carcinomas were located in the head of the pancreas, including two with multiple small calcifications in the entire pancreas and one with a solitary large calcification in the head. Another pancreas body carcinoma was associated with diffuse small calcifications both in and distal to the mass. In three pancreatic carcinomas, pancreatic calcification was demonstrated proximal and distal to the pancreatic carcinomas. All four patients died within 14 months after the clinical diagnosis of pancreatic carcinoma. Although we cannot draw a definitive conclusion on the link because of the limited number of cases in this retrospective study, followup studies on patients with chronic calcifying pancreatitis are needed for clarification.


Acinar cell carcinoma of the pancreas. Report of two cases with complex histomorphologic features causing diagnostic problems.

Two pancreatic acinar cell carcinomas with distinctive morphologic features are described. Both tumors showed a variable combination of different histomorphologic patterns formed by tumor cells in different degrees of acinar differentiation. They caused diagnostic problems involving differential diagnosis from normal pancreas and from mixed acinar-endocrine tumor. The presence of mitosis, nuclear atypia, and tumor necrosis are helpful for recognizing its neoplastic nature, and the ultrastructural finding of zymogen-like but not neurosecretory granules prevented the misdiagnosis of a mixed acinar-endocrine tumor. Immunohistochemical studies revealed variable immunostaining patterns corresponding to different types of tumor cell present. Both tumors were found to be aneuploid by flow cytometric DNA study. Our study confirmed previous observations that pancreatic acinar cell carcinomas are highly malignant tumors in spite of the fact that they can differentiate into highly differentiated acinar cells.


Adenocarcinoma of the pancreas coexisting with pancreatic abscess.

Of 20 patients treated for pancreatic abscess during the years 1984-1991, two patients were found to have adenocarcinoma of the pancreas associated with their pancreatic abscesses. In one patient an adenocarcinoma of the proximal pancreas caused ductal obstruction, which may have been the primary cause of an abscess distal to the tumor. In the second patient, metastatic adenocarcinoma of the pancreas and a concurrent pancreatic abscess were found when the patient's abdomen was explored for complications related to gallstone pancreatitis. In both patients, the tumor was unresectable at presentation. A detailed review of these cases is presented as well as a review of the related literature.


Acute pancreatitis associated with milk allergy.

We are reporting the case of a 23-yr-old patient who had recurring episodes of acute pancreatitis characterized by the typical abdominal pain, elevated serum levels of pancreatic enzymes, and enlargement of the pancreas and edema on sonogram. These episodes were accompanied by facial erythema with conjunctival injection, generalized pruritus, diarrhea, and eosinophilia, and they were induced by the consumption of milk. The serum levels of IgE specific to cow milk proteins and to beta-lactoglobulin were increased. We suggest that these episodes are caused by a milk allergy (milk), that has been described as an unusual cause of acute pancreatitis.


Factors associated with closed head injury in a pediatric population.

The purpose of this study was to identify characteristic factors in children who sustained closed head injury (CHI) between birth and less than 15 years of age. A two-year retrospective audit of charts from a large metropolitan pediatric hospital with a trauma center yielded a sample of 138 charts that met the established criteria for inclusion in the study. Using a descriptive design, data were gathered on age, sex, race, cause of injury, severity of injury, season of accident, time of accident and length of hospital stay. Data analysis revealed that males were 1.5 times more likely to sustain CHI than females. Both sexes showed the highest incidence of CHI during the first year with a second less dramatic peak at around 6 years of age. Transportation-related causes accounted for 57.2% of the injuries with falls accounting for another 22.5%. Of the transportation-related injuries, 27.5% were associated with motor vehicle accidents. The lack of restraint use for subjects in the motor vehicle accident group was associated with 5 deaths as opposed to no deaths in subjects who were restrained. Over 70% of the injuries occurred in the time periods of 2:00-6:00 p.m. (31.9%) and 6:00-10:00 p.m. (40.7%). CHI occurred less frequently in the winter (13.8%) than any other season. Using the Glasgow Coma Scale scores, 56.5% of the injuries were categorized as mild, 17.4% were moderate and 26.1% were severe. There was an 8% mortality rate secondary to injury in the sample.


Traumatic brain injury: a family experience.

Traumatic brain injury (TBI), sometimes referred to as a silent epidemic, affects thousands of people each year. A head injury not only affects the patient, but the entire family system as well. Families experience a myriad of needs during this time of crisis. With the immediate focus on the patient's physical or cognitive state, the family's needs may go unnoticed or unrecognized. It is imperative health care professionals understand the emotional impact on family needs, and the unique grieving patterns which influence their ability to cope with this situation. Caregivers are advised to assess, formulate and implement a plan of care for the family as well as the patient. Since families play such an integral role in the patient's recovery process, it is crucial to recognize the scope of the TBI experience and provide care within the context of the individual family system.


Head injury: impact on the wives.

Wives of head-injured patients often need considerable support because of the myriad of role transitions and role changes they experience. The impact of the head injury on the wife of a survivor is presented in this article. Content analysis was used to analyze data with the themes of role changes, emotional impact of the injury, hope and need for support emerging. Implications for practice and research include need for support groups with nurses as facilitators, the importance of fostering hope, and need for education of health care professionals.


Occupational stress in neurosurgery: an exploratory study.

Occupational stress in nursing has been a popular topic for investigation. In particular, comparisons between practice areas such as the intensive care unit (ICU) and medical-surgical unit have attempted to identify what factors are stressful, and whether some nursing environments are more stressful than others. Such studies have led to inconclusive findings. While many practice areas have been studied, the neurosurgical ICU and neuromedical/neurosurgical units have largely been overlooked. Using interviews, this exploratory study examined aspects of nursing perceived as stressful by staff members working in ICU and medical-surgical units in a neuroscience center. Findings suggested that patient care, communication, workload, management and supervision, organizational and personal circumstances are major sources of stress. These findings are in keeping with studies of stress conducted in national and international non-neurosurgical nursing practice areas.


Chronobiological aspects of epileptic phenomena: a literature review, implications for nursing and suggestions for research.

Every physiologic and psychologic variable studied heretofore demonstrates rhythmic fluctuations. Chronobiology is the field of study which examines these fluctuations. Chronobiology is highly significant to nursing practice, since human responses are affected by these rhythmic fluctuations. A review of the literature produced little information on epilepsy chronobiology. The status of research in epilepsy chronobiology remains at the basic science level. Continued research is a priority before nursing can use epilepsy chronobiology knowledge in the clinical setting.


Purple glove syndrome: a complication of intravenous phenytoin.

Intravenous phenytoin, available for use since 1956, has several well known adverse effects, such as hypotension, arrhythmias and toxicity. Purple glove syndrome is a less common complication that can have serious consequences. Fasciotomies, amputations and permanent disuse of the hand and forearm have been reported. The etiology of purple glove syndrome is still unknown, but possible etiologies and risk factors have been suggested. Three stages of purple glove syndrome have been identified: appearance, progression and resolution. During the second stage, progression, purple glove syndrome can be identified as either mild or severe. Mild cases may heal uneventfully when nursing measures such as elevation, application of dry, gentle heat and measures to prevent secondary injury are instituted. Severe cases may require emergency surgical intervention such as fasciotomy to relieve pressure and restore blood flow. Therapeutic nursing interventions aimed at maximizing healing and promoting comfort are essential.


Powerlessness and the patient under neuromuscular blockade.

The patient under neuromuscular blockade is dependent on members of the interdisciplinary team for all physical and psychological needs. Loss of control leads to feelings of powerlessness and helplessness which can adversely affect the patient's ability to cope. The nurse caring for this patient must be able to effectively combine clinical expertise with compassion in order to most effectively help the patient cope with the period of powerlessness. An individualized approach to restore control helps curtail the progression of powerlessness to hopelessness and limit the associated depression and anxiety.


Clinical applications of brain death protocols.

The declaration of death by neurological criteria has become more commonly accepted and used within the medical community, especially within the past 10 years. There remains, however, a great deal of misunderstanding and lack of awareness among health care professionals as to the criteria used to determine brain death and the importance of adhering to brain death determination protocols. Youngner et al, in their 1989 survey, found more than one-third of surveyed physicians involved in the decision-making process for brain death were still unable to correctly identify and apply the whole brain criteria needed to determine brain death. To some degree, this unfamiliarity can perhaps be explained by the infrequency with which brain death occurs. Physicians and nurses are usually not involved in brain death pronouncements more than a few times each year. Because of this, hospitals need to develop and maintain brain death protocols which are in keeping with the most current scientific literature and accepted medical practice.


Expert systems and expert behavior.

Iliad 4.0 and QMR 2.03 are computer-based diagnostic knowledge bases that can play many roles in decision support and other areas of medical practice, but neither appears ready to assume the role of an expert diagnostic consultant. In contrast to human experts, these programs have problems related to recognition of their own limitations, interpretation of continuous data, recognition of dependent findings, selection of tests, and description of the impact of certain tests. Suggestions to improve these aspects of knowledge bases are offered.


Computer-assisted test interpretation: considerations in patient care.

Computer-assisted test interpretation (CATI) is a set of developing technologies designed to support medical decision-making. This paper develops a taxonomy of computer-assisted test interpretation, giving specific consideration to the characteristics of the data that are to be interpreted, the nature of the interpretive task, the expected involvement of the health professional in the generation of the interpretation, the inference mechanism used for the interpretation, and the broader context of the interpretation. We go on to examine potential benefits and disadvantages of CATI systems in terms of accuracy, information management, interpretation time, patient management, medical communication, and expense. Finally, we examine electrocardiogram interpretation systems from the perspective of this taxonomy, and offer suggestions regarding areas of further inquiry into the effects of CATI on medical care.


Regional variation in VAMC's operative efficiency.

The Department of Veterans Affairs is managed by a global budget regulated by Congress. How effective the VA handles this budget can provide insight into future plans for any form of universal health insurance. Using Date Envelope Analysis (DEA) this study shows that 51 of 158 continental VAMCs operate relatively efficiently. Variation in operative efficiency could be explained by Service Area size and geographic regional location. This finding suggests more active regional planning may improve veteran hospital operative efficiency.


Using an artificial neural network to diagnose hepatic masses.

Using abdominal ultrasonographic data and laboratory tests, radiologists often find differential diagnoses of hepatic masses difficult. A computerized second opinion would be especially helpful for clinicians in diagnosing liver cancer because of the difficulty of such diagnoses. A back-propagation neural network was designed to diagnose five classifications of hepatic masses: hepatoma, metastatic carcinoma, abscess, cavernous hemangioma, and cirrhosis. The network input consisted of 35 numbers per patient case that represented ultrasonographic data and laboratory tests. The network architecture had 35 elements in the input layer, two hidden layers of 35 elements each, and 5 elements in the output layer. After being trained to a learning tolerance of 1%, the network classified hepatic masses correctly in 48 of 64 cases. An accuracy of 75% is higher than the 50% scored by the average radiology resident in training but lower than the 90% scored by the typical board-certified radiologist. When sufficiently sophisticated, a neural network may significantly improve the analysis of hepatic-mass radiographs.


Development of a diagnostic and therapeutic simulation system based on patient data and specialist's knowledge. I. Simulation of diagnostic process.

A new simulation system of diagnostic and therapeutic processes is developed. The aim is to train medical students for the practical use of their knowledge, utilizing patient data in a total hospital information system. The knowledge in the system is presented by the specialists for every case. In medical school there are many specialists in various fields. With their cooperation the system can grow up to a comprehensive CAI system for clinical education. The system is designed to work on the mainframe for easiness of development, maintenance and extensions of the system. The present framework has been applied to the simulation of diagnostic process. The usefulness of the present system has been confirmed by specialists and students.


Microleakage--full crowns and the dental pulp.

Recent studies have described microleakage under full crowns cemented with several different cements. This study tested three different types of crown margin preparations--a chamfer, a shoulder, and a shoulder plus a bevel to determine whether or not the margin preparation could affect microleakage. All crowns were cemented with zinc phosphate cement. The crowns were tested for leakage in thermocycled dye. All crowns demonstrated significant leakage following the path of the dentinal tubules into the pulp. This could possibly be one of the causes of pulpal inflammation and even pulpal death under full crowns.