Antibiotics

Clin Obstet Gynecol, 1991 Dec, 34(4), 730 - 41
Management of preterm premature rupture of membranes; Asrat T et al.; The variables enumerated in the preceding paragraphs and the constantly changing and improving technology in neonatal care mean that the data on which to base the best management plans of PPROM are not yet available . Rather, we must be willing to revise our approach to the treatment of this entity constantly as new information is found . However, several important changes in the management of these patients over the last few years were implemented and have had a significant impact on the outcome of these neonates . The use of routine prophylactic intrapartum amnioinfusion is one of these . Although preliminary, the data on prophylactic antibiotic use are promising and have brought us closer to the concept of treating occult intraamniotic infections with antibiotics rather than immediate and indiscriminate delivery . The identification of several factors such as interleukin-1, neutrophil activating peptide-1/interleukin-8, and tumor necrosis factor (TNF) in patients with idiopathic preterm labor may allow us to determine the pathophysiologic mechanism by which preterm labor leading to PPROM is initiated and allow us to tailor treatment specifically . For instance, in such patients, uterine activity may respond to antibiotic therapy rather than the usual tocolytics . Unfortunately, measurements of such factors are not yet widely available and remain primarily research tools . However, these recent findings give us a glimpse of what lies ahead . It is entirely conceivable that a symposium on the management of PPROM eventually will have a section devoted to its prevention that is based on an understanding of its pathophysiology.

Eur J Pediatr Surg, 1991 Dec, 1(6), 335 - 8
The effect of steroid treatment on corrosive oesophageal burns in children; Keskin E et al.; A retrospective study was done on corrosive oesophageal burns to ascertain the preventive effect of corticosteroids on stricture development . Within the last 12 years 351 children were admitted to our medical centre with a history of corrosive agent ingestion . In 235 of these the diagnosis of oesophageal burn was confirmed by means of oesophagoscopy . Children admitted within the first 48 hours received steroid, antibiotic and fluid therapy while fluid and antibiotics were given, if needed, in the rest . Forty-six of the children were lost to follow-up . The type of corrosive agent, the admission period, the degree of the burn and the stricture development were used as parameters . Stricture development was found statistically significant in late admitted patients vs . early admissions . This retrospective study suggests the effectiveness of corticosteroid treatment in preventing the stricture development.

Rev Fr Gynecol Obstet, 1991 Dec, 86(12), 731 - 5
{Selective salpingography and tubal interventional radiography}; Rouanet JP et al.; The study involved 70 patients considered to be sterile and in whom hysterosalpingography showed no tubal passage . Selective catheterisation enabled opacification under pressure in more than 80 p . cent of cases, with perfect visualisation of the entire tubes and significant peritoneal passage . In the presence of obstructive stenosis, disobstruction-reacanalisation using a soft probe was attempted with success in more than one case out of two . Future perspectives of selective salpingography appear to be very large . This technique seems to have a large number of indications apart from transport problems: recanalisation, sterilisation, and tubal antibiotic sensitivity studies.

J Otolaryngol, 1991 Dec, 20(6), 400 - 3
Orbital complications of ethmoiditis: B.C . Children's Hospital experience, 1982-89; Samad I et al.; Orbital complications of ethmoiditis primarily affect children . Infection proceeds through contiguous spread to the orbit . We undertook a retrospective analysis of all children admitted to British Columbia Children's Hospital in Vancouver with a diagnosis of periorbital and orbital cellulitis due to ethmoiditis between 1982 and 1989 . The majority of children presented with periorbital cellulitis, which resolved with aggressive parenteral antibiotic therapy . Five children (17%) progressed to subperiosteal abscess formation as documented by CT scan and required external ethmoidectomy as a drainage procedure . We conclude that early hospitalization and aggressive parenteral antibiotics are effective in resolving periorbital cellulitis . Surgical drainage is indicated when subperiosteal abscess is documented by CT scan . In our series, there were no cases of permanent visual deficit resulting from complications of ethmoiditis.

J R Coll Surg Edinb, 1991 Dec, 36(6), 381 - 3
Management of mammillary fistulae; Bundred NJ et al.; Mammillary fistulae develop between the lactiferous ducts of the breast and areolar skin . Over a 14-year period 41 fistulae were treated in 36 patients (34 women, 2 men) . In 24 women at least one subareolar abscess (mean 2.5) had been incised and drained previously . Fourteen fistulae developed after discharge of an inflammatory mass and three after surgical biopsy . Twelve women underwent 13 fistulectomies, two of which required reoperation . The remaining 24 patients with complicated fistulae (n = 28) had previously undergone multiple surgical procedures; 12 patients had 13 fistulae treated by total duct excision and primary closure without antibiotic cover and six fistulae required reoperation . Fifteen fistulae in 12 women were treated by duct excision with either primary closure under antibiotic cover (n = 7) or packing with healing by granulation (n = 8) and only one recurred (P less than 0.05) . Operations for mammillary fistulae should be treated as contaminated procedures . In simple cases where no previous surgery has taken place, fistulectomy is appropriate . In complicated cases, treatment should be duct excision with the wound either closed primarily under antibiotic cover or left open to heal by secondary intention.

Clin Radiol, 1991 Dec, 44(6), 422 - 4
Case report: percutaneous drainage of periappendiceal actinomycosis; Goldwag S et al.; Abdominal actinomycosis is a disorder which often complicates a chronic perforation of the gastrointestinal (GI) tract, such as at the appendix (Wyngaarden and Smith, 1988) . Delayed diagnosis characterizes abdominal actinomycosis . Multiple abscesses and draining sinuses are frequently present . Treatment has consisted of long-term oral antibiotic therapy coupled with surgery, including incision and drainage of abscesses with removal of persistent sinuses (Berardi, 1979) . We present a patient with abdominal actinomycosis complicating a chronically ruptured appendix who was managed by percutaneous catheter drainage and antibiotic therapy.

Pediatr Infect Dis J, 1991 Dec, 10(12), 923 - 8
Serum C-reactive protein in childhood meningitis in countries with limited laboratory resources: a Chilean experience; Roine I et al.; Quantitative C-reactive protein (CRP) was determined sequentially by nephelometry and photometry from a finger prick serum sample in 67 children with bacterial meningitis (BM) and 16 children with aseptic meningitis (AM) . The initial mean CRP value of 180 mg/liter in children with BM differed significantly from the 12 mg/liter found in those with AM (P less than 0.001) . In BM a slow descent instead of rapid normalization or a secondary increase in sequential CRP values were early indicators of complications during recovery, such as resistance to the antibiotic . A significant difference in the mean CRP values between uneventful and complicated courses of BM was observed from the fourth day on (P less than 0.001) . The measurements obtained with nephelometry correlated reliably with the more widely available photometry (r = 0.99) . Easily performed rapid CRP determinations can considerably improve the quality of care in meningitis patients, especially in those situations where facilities for performing bacterial cultures or antibiotic susceptibility testing are not available.

Jpn Circ J, 1991 Dec, 55(12), 1228 - 32
Infective endocarditis causing acute myocardial infarction by compression of the proximal left coronary artery due to a mycotic aneurysm of the sinus of Valsalva; Koike S et al.; An extremely unusual case of myocardial infarction associated with infective endocarditis (IE) is described . A 38-year old male with a high fever was transferred to our hospital for further treatment of IE . Two-dimensional echocardiogram showed a large mycotic aneurysm of the sinus of Valsalva in contact with neighbouring structures . The patient had a rapid recovery within several days after administration of antibiotic agents . However, he then developed abrupt onset of severe precordial pain . From the echocardiogram images and biochemical evaluation he was diagnosed as having an acute subendocardial infarction . Serial echocardiograms revealed expansion of the aneurysm, extending from the myocardium of the anterolateral free wall to the lower margin of the proximal left coronary artery . The cause of acute myocardial infarction was thought to be incomplete occlusion of the coronary artery through compression by the enlarging mycotic aneurysm of the sinus of Valsalva . Urgent surgery confirmed compression of the left coronary artery by the large mycotic aneurysm as the cause of acute myocardial infarction.

Clin Pharmacol Ther, 1991 Dec, 50(6), 682 - 7
Influence of rifampin on the pharmacokinetics of pefloxacin; Humbert G et al.; Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections . The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers . Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period . During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d . oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day . The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05) . The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05) . The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A . This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Am J Med, 1991 Dec, 91(6), 625 - 30
Frequent occurrence of asplenism and cholelithiasis in patients with autoimmune polyglandular disease type I; Friedman TC et al.; PURPOSE: This study assesses the occurrence of asplenism and gallstones in patients with autoimmune polyglandular disease type I (APG I) . PATIENTS AND METHODS: Nine patients with APG I (ages 14 to 48) were studied at the National Institutes of Health . Each patient received endocrine testing, a careful examination of his or her peripheral blood smear, lymphocyte immunophenotyping, a liver-spleen scan, and either an upper abdominal ultrasound or a computer-assisted tomogram to evaluate the spleen and gallbladder . RESULTS: We documented asplenism in four patients and cholelithiasis in four patients, with two patients having both conditions . The patients with asplenism had Howell-Jolly bodies on peripheral blood smears, lack of splenic uptake by liver-spleen scan, and absent spleens by abdominal computed tomographic scan or ultrasound evaluation . The clinical presentation of the patients with cholelithiasis ranged from acute symptoms requiring surgery to asymptomatic gallstones . Lymphocyte immunophenotyping did not reveal consistent changes in either B- or T-cell subpopulations in the patients studied . CONCLUSION: Asplenism and gallstones occur frequently in patients with APG I . In addition to careful examination of the peripheral blood smear for Howell-Jolly bodies to screen for asplenism, we recommend an abdominal ultrasound to detect asplenism and/or gallstones in all patients with APG I . Appropriate immunizations and antibiotic coverage may be helpful in those patients with absent spleens.

J Trauma, 1991 Dec, 31(12), 1579 - 83
Management of transperitoneal gunshot wounds of the spine; Kihtir T et al.; To evaluate the results of a conservative approach to gunshot wounds of the spine with a transperitoneal trajectory, we analyzed our 4-year experience with 21 patients . The management protocol consisted of standard treatment of the intra-abdominal injuries, vigorous irrigation of the missile track, and a 48-hour course of antibiotic therapy . The lumbar spine was involved in 14 patients (67%) and the thoracic spine was injured in seven (33%) . Eleven patients (52%) were paraplegic on admission and ten patients (48%) had a fixed partial neurologic deficit . One patient with an ISS of 75 died intraoperatively from exsanguination (mortality, 5%) . Early morbidity correlated with ISS greater than 40 and spinal AIS greater than 3 . Late nonneurologic morbidity was independent of ISS and spinal AIS . One patient required reoperation for a retroperitoneal abscess secondary to a leak from a repaired ureter . Another patient had a retroperitoneal collection on a CT scan which resolved spontaneously . There were no spinal or paraspinal infectious complications in the presence (five cases) or absence of a colonic injury . No change in neurologic status was observed in any patient during a mean follow-up period of 3 months . This preliminary experience suggests that a conservative approach consisting of irrigation of the missile track and short-term antibiotic therapy without laminectomy or removal of fragments from the spinal canal yields optimal results without increasing infectious complications of the spine.

Am Surg, 1991 Dec, 57(12), 803 - 5
Wound infection in patients with traumatic small intestinal injuries; Strasen KM et al.; Delayed closure has been the traditional management of wounds in patients with traumatic colon injury, whereas small bowel injury has generally been treated with primary wound closure . Sixty-seven patients with traumatic hollow viscus injury isolated to jejunum and ileum were reviewed to determine the incidence of septic wound complications . Fifty-eight patients underwent primary wound closure with 15 (26%) developing wound infections . Nine patients had their wounds left open because of major intraperitoneal contamination with no resulting wound infection . In patients with primary closure of their wounds, there was no difference between these developing wound infections and those without with regard to the presence of hypotension, amount of spill, type of repair, site of injury, or antibiotic given . Significant difference was present regarding time between injury and surgery (8.6 vs 17.7, P = .025) . Results suggest that delayed wound closure should be performed in patients with traumatic small bowel injury.

J Struct Biol, 1991 Dec, 107(3), 250 - 8
A preliminary scanning tunnelling microscopy study of the surface-organised structures of gramicidin S hydrochloride on highly oriented pyrolytic graphite; Brown NM et al.; For an initial study of potentially surface-structural self-organising systems of biological significance by scanning tunnelling microscopy (STM), gramicidin S, a pseudocentrosymmetric cyclodecapeptide with antibiotic properties, was chosen as prototype, recognising its structure as having both intramolecular and intermolecular hydrogen-bond forming propensity . The surface-organised structures, based on gramicidin S hydrochloride deposited on a highly oriented pyrolytic graphite (HOPG) substrate, have been observed by STM in air under ambient conditions . These are characterised in the main by rectangular or rectangle-like structural elements identified with the individual gramicidin S hydrochloride molecules . Two kinds of arrangements of gramicidin S hydrochloride in a two-dimensional array are found, i.e., as a centred rectangular lattice and a primitive rectangular lattice . The STM topographical arrays and the molecular dimensions obtained are in good quantitative agreement with the corresponding X-ray crystallographic data . The differences between the STM results, the theoretical models, and the X-ray crystallographic data are attributed to the intermolecular interactions present in the three-dimensional gramicidin S crystal but absent in the lower dimensional arrays and to the environments in which a gramicidin S hydrochloride molecule finds itself during deposition and drying on the HOPG substrate.

Breast Cancer Res Treat, 1991 Dec, 20 Suppl, S15 - 23
Dose-intensive treatment of breast cancer supported by granulocyte-macrophage colony-stimulating factor (GM-CSF); Neidhart JA; Substantial intensification of chemotherapy doses is a promising approach to the treatment of refractory malignancy currently receiving increasing attention . For the past 4 years we have used 3 repeated cycles of a combination of cyclophosphamide (5 g/m2), etoposide (1500 mg/m2), and cisplatin (150 mg/m2) without replacement of progenitor cells and with and without colony-stimulating factor support . The duration of threatening levels of granulocytopenia with this regimen averages 10.2 days, although an occasional patient has prolonged recovery (range, 5-20 days) and most patients require antibiotic therapy for cytopenic fever . We have not yet identified the optimal dose of GM-CSF, but 500 micrograms/m2 significantly shortens the duration of cytopenia (ANC less than 300/mm3) to 5.9 days with a resultant decrease in incidence and duration of cytopenic fever (from 10.8 to 1.7 days), use of antibiotics (from 10.8 to 7.6 days), and duration of hospitalization (from 22.2 to 16.3 days) . Seventeen patients with metastatic breast cancer have received this regimen to date with a 35% complete response (CR) rate and a 53% partial response (PR) rate . Most of these patients were refractory to standard therapy . Four of six (67%) not refractory to standard therapy have achieved complete responses that are ongoing at 3.5 to 10.4 months . We conclude that dose-intensive therapy is an option that needs more careful exploration early in the treatment of advanced breast cancer and that GM-CSF decreases morbidity and risk of dose-intensive regimens.

J Formos Med Assoc, 1991 Dec, 90(12), 1179 - 85
Treatment of open femoral and tibial shaft fractures preliminary report on external fixation and secondary intramedullary nailing; Wu CC et al.; From January 1987 to May 1989, a total of 38 adult cases were treated with 15 femoral and 25 tibial shaft shifting procedures from external fixation to reamed intramedullary nailing and followed up for at least 1 year (average, 23 months) at the authors' institution . The indications for the shifting procedures included routine sequential femoral external fixation and failed tibial external fixation treatment such as loss of reduction, atrophic healing process and inability of patients to tolerate casting . The delay period for the shifting procedure was 5 days in the femur and 48 days in the tibia . The union rate for the femur was 93% (14/15), and the tibia, 96% (24/25) . The union period after the shifting procedure was 4.8 +/- 1.7 months in the femur, and 5.2 +/- 1.8 months in the tibia . Range of motion of the knee and ankle were satisfactory . Deep infection was the most serious complication, and the tibia was involved more often than the femur (20% to 13%) (p greater than 0.05) . The most favorable management of deep infection was local drainage till bony union . We conclude that a shifting operation can be considered as one of the alternative procedures for several femoral or tibial shaft open fractures after fixation with external fixation . Wound and pin tract care, a shorter period of external fixation, a longer delay period before nailing, and perioperative antibiotic use may significantly lessen the infection rate.

Bioorg Khim, 1991 Dec, 17(12), 1689 - 93
{Structure-functional studies of polymyxins . (1)-NMR analysis of polymyxin B and M conformation}; Okhanov VV et al.; Spatial structures of two polymyxin antibiotics are compared by means of one- and two-dimensional 1H NMR spectroscopy . Cyclic parts of polymyxins B and M contain a system of hydrogen bonds including two beta-turns, however, the analysis of coupling constants 3JHN-C alpha H demonstrated that torsional angles phi of peptide bonds of the residues forming beta-turns in polymyxin M depend on the type of the anion . An increase in lability of the polymyxin M cyclic part in comparison with polymyxin B correlated with the selective cleavage of the peptide bond Dab8-Dab9 of this antibiotic with subtilisin . A similar correlation was found for a short analogue of polymyxin B, a cycloheptapeptide.

Mol Gen Genet, 1991 Dec, 231(1), 113 - 23
Genetics of streptomycin production in Streptomyces griseus: molecular structure and putative function of genes strELMB2N; Pissowotzki K et al.; The nucleotide sequence of a 5.1 kb fragment from the streptomycin biosynthetic gene cluster from Streptomyces griseus revealed the presence of five open reading frames which form part of two convergently oriented transcription units strDEL and strNB2M . The coding capacity for polypeptide products was calculated to be 35.7 kDa (StrE), 32.2 kDa (StrL), 35.6 kDa (StrN), 38.2 kDa (StrB2), and 21.9 kDa (StrM), respectively . Various observations suggested that the gene products StrD (dTDP-glucose synthase), StrE (dTDP-glucose dehydratase), StrM (dTDP-4-keto-6-deoxyglucose 3,5-epimerase), and StrL (dTDP-dihydrostreptose synthase) are involved in biosynthesis of the streptose moiety of streptomycin . StrE and StrL are significantly similar in primary structure to each other and to other oxidoreductases (epimerases) involved in hexose metabolism . Genes for dTDP-glucose synthase and dehydratase occur in other gene clusters for antibiotic production . Therefore, the strD and strE genes could serve as universal probes indicative of the presence of biosynthetic capacity for 6-deoxyhexose moieties . The StrB2 protein showed 69% amino acid identity to the first-step amidinotransferase StrB1 . The presence of both strB genes appears to be the result of a gene duplication event . The gene product StrN contains sequence motifs also conserved in the putative catalytic and/or substrate recognition domains of aminoglycoside phosphotransferases and eucaryotic protein kinases . The possible role of a TTA codon, located near the start of the strN reading frame, in regulation of the str cluster is discussed.

J Cell Physiol, 1991 Dec, 149(3), 548 - 59
Gene activation mediated by protein kinase C in human macrophage and teratocarcinoma cells expressing aminoglycoside phosphotransferase activity; Maio JJ et al.; The bacterial neomycin phosphotransferase gene driven by the Moloney mouse leukemia virus long terminal repeat (LTR) or SV40 early region promoter was introduced into the human promonocyte-macrophage cell line, U937, and into the pluripotential human embryonic teratocarcinoma cell line, NT2/D1 . Clonally derived cell lines capable of growing in 2-4 mg/ml of the aminoglycoside antibiotic, G418 (Geneticin), were established and transfected with pHIVCat, a plasmid expressing the bacterial chloramphenicol acetyl transferase (CAT) activity under the control of the human immunodeficiency virus (HIV-1) LTR . All of the G418 resistant (neo(r)) U937 cell lines and 10 of 14 neo(r) NT2/D1 cell lines exhibited reduced basal levels of CAT expression or impaired responses to activation of the HIV-1 LTR by phorbol 12-myristate 13-acetate (PMA) when compared to the parental lines . Other differences included inhibition of tat activation of the HIV-1 LTR and increased sensitivity of U937 cells to human tumor necrosis factor alpha . The expression of other eukaryotic promoters including the HTLV-1 LTR, SV40 ori sequences, and the human beta-actin gene promoter was similarly affected . However, differentiation of the neo(r) U937 cells into macrophages was neither delayed nor impaired . Because PMA is an activator of protein kinase C (PKC) and a potent inducer of HIV-1 directed gene expression, the amounts, sensitivity to G418, and cytosol to membrane translocation of this enzyme were determined in the wild type and neo(r) U937 cells . G418 at concentrations too low to affect cell growth (12-150 micrograms/ml) inhibited PMA-induced transactivation responses in wild type cells but did not inhibit PKC-dependent protein phosphorylation in vitro . PKC activities in the wild type and neo(r) cells were similar in absolute amounts and in the cytosol-membrane distribution of the enzyme . In contrast with wild type cells, however, all of the cytosolic Ca(2+)-phospholipid-dependent form of PKC disappeared from the neo(r) cells within 30 min after PMA induction . The results suggested that, depending upon the cell type, gene cotransfer using aminoglycoside resistance as a selectable marker may seriously perturb important cellular control mechanisms such as the PKC pathway leading to activation of gene expression.

Proc Natl Acad Sci U S A, 1991 Dec 1, 88(23), 10535 - 9
Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin; Ashkenazi A et al.; Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, and cytotoxic effects . During bacterial infection of the bloodstream (sepsis), TNF-alpha induction by bacterial endotoxin is thought to be a major factor contributing to the cardiovascular collapse and critical organ failure that can develop . Despite antibiotic therapy, these consequences of sepsis continue to have a high mortality rate in humans . Here we describe a potent TNF antagonist, a TNF receptor (TNFR) immunoadhesin, constructed by gene fusion of the extracellular portion of human type 1 TNFR with the constant domains of human IgG heavy chain (TNFR-IgG) . When expressed in transfected human cells, TNFR-IgG is secreted as a disulfide-bonded homodimer . Purified TNFR-IgG binds to both TNF-alpha and TNF-beta and exhibits 6- to 8-fold higher affinity for TNF-alpha than cell surface or soluble TNF receptors . In vitro, TNFR-IgG blocks completely the cytolytic effect of TNF-alpha or TNF-beta on actinomycin D-treated cells and is markedly more efficient than soluble TNFR (24-fold) or monoclonal anti-TNF-alpha antibodies (4-fold) in inhibiting TNF-alpha . In vitro, TNFR-IgG prevents endotoxin-induced lethality in mice when given 0.5 hr prior to endotoxin and provides significant protection when given up to 1 hr after endotoxin challenge . These results confirm the importance of TNF-alpha in the pathogenesis of septic shock and suggest a clinical potential for TNFR-IgG as a preventive and therapeutic treatment in sepsis.

Brain Res, 1991 Nov 29, 565(2), 345 - 8
D-cycloserine, a putative cognitive enhancer, facilitates activation of the N-methyl-D-aspartate receptor-ionophore complex in Alzheimer brain; Chessell IP et al.; The action of D-Cycloserine (DCS) at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex has been studied with membranes from inferior parietal cortex of patients with Alzheimer's disease . The maximal response of the site, measured using {3H}MK-801 binding, was 64% of that observed with glycine . Stimulation of binding induced by DCS in the presence of fixed concentrations of glycine resulted in a family of dose-response curves, consistent with the antibiotic having the property of a partial agonist at this glycine site . It is proposed that because of circumscribed glutamatergic pyramidal cell pathology DCS will have benefit for Alzheimer's patients over and above all other types of cognitive impairment.

N Z Med J, 1991 Nov 27, 104(924), 488 - 90
Cost analysis of a major burn; Lofts JA; A retrospective review was undertaken of 26 patients admitted to Middlemore Hospital between January 1986 to July 1989 with burns totalling more than 30% of total body surface area . An attempt was made to estimate the total cost of successful inpatient management of a major burn using known and assumed values . The new schedule of interboard hospital charges was also employed for greater accuracy . The 20 survivors had a mean initial hospital stay of 68.7 days at a cost of between $37,077 and $40,702 (1989 values) and $46,069 (1991 values) . This latter figure equates to an average cost of $647 per patient per day or, alternatively, $927 per % burn . Suggestions to reduce costs and improve treatment include: earlier excision and grafting; the establishment of a regional skin bank and keratinocyte culture facility to aid wound closure; and guidelines on antibiotic prescribing.

Am J Ophthalmol, 1991 Nov 15, 112(5), 543 - 7
Treatment of infectious scleritis and keratoscleritis; Reynolds MG et al.; We reviewed 28 cases of culture-proven infectious scleritis and keratoscleritis to clarify the role of an operation in this disorder . Surgical management in 11 patients with keratoscleritis included cryotherapy, five; penetrating corneal-scleral graft, two; lamellar corneoscleral graft, two; and tectonic penetrating keratoplasty, two; in addition to intensive fortified antibiotic eyedrops . Eight patients with keratoscleritis were treated medically only with intensive fortified frequent antibiotic eyedrops, one; intensive instilled plus intravenous antibiotics, three; and instilled, intravenous, and subconjunctival antibiotics, four . Seven of eight patients treated with antibiotics alone and two of 11 patients who received surgical intervention in addition to antibiotics eventually required evisceration or enucleation of the eye . These results suggest that cryotherapy, lamellar or penetrating corneoscleral graft, in addition to intensive antibiotic therapy, may improve the outcome of patients with infectious keratoscleritis . Five eyes with isolated scleritis without corneal involvement were treated with conjunctival recession and cryotherapy in addition to aggressive antibiotics, and four were treated with antibiotics alone . The infections of these nine patients resolved.

Postgrad Med, 1991 Nov 15, 90(7), 51 - 2, 55-60
Ocular trauma . Triage and treatment; Janda AM; Many types of ocular trauma can be diagnosed and treated in the primary care office, particularly if a slit lamp is available . Treatment for corneal abrasions consists of applying a cycloplegic medication, antibiotic ointment, and a patch (unless a corneal ulcer is suspected) . Iritis can be treated with cycloplegics and topical corticosteroids; the prescribing physician should be familiar with the potential ocular side effects and complications . Hyphemas are treated with bed rest, topical atropine sulfate drops and topical corticosteroids, as well as measures to prevent rebleeding . A slit lamp, topical anesthesia, and a foreign-body spud greatly facilitate the removal of foreign bodies from the cornea . Acid and alkali burns should be irrigated until the pH is normal and then should be treated like a corneal abrasion . Lid lacerations must be repaired with care to preserve proper functioning of the lid . Ruptures of the globe are serious injuries requiring surgical repair and long-term follow-up.

Biochem Biophys Res Commun, 1991 Nov 14, 180(3), 1403 - 7
The ble gene of Streptoalloteichus hindustanus as a new selectable marker for Dictyostelium discoideum confers resistance to phleomycin; Leiting B et al.; An expression cassette has been constructed which allows expression of the ble gene isolated from Streptoalloteichus hindustanus in Dictyostelium discoideum . This construct has been shown to confer resistance to the bleomycin related antibiotic phleomycin . since the uptake of phleomycin by the cells is pH dependent, we established conditions that allow selection of phleomycin-resistant transformants . Vectors pfeI and pfeII contain, in addition to the cassette, a 592 bp fragment of the D . discoideum plasmid Ddp2 that enables the plasmids to replicate extrachromosomally in Dictyostelium when transformed into a strain that expresses a Ddp2-specific transacting factor (12) . pfeI and pfeII contain various unique restriction enzyme sites for cloning . They differ in the G/C-content of the sequence upstream of the ATG start codon.

Biochem Biophys Res Commun, 1991 Nov 14, 180(3), 1342 - 9
Dactinomycin is a competitive neurokinin-2 receptor antagonist; Delay-Goyet P et al.; Dactinomycin, a peptide antibiotic from Streptomyces spp., is a classical agent which inhibits DNA replication . In the present study, dactinomycin inhibited specific {125I}NKA binding in rat colon membranes (KI = 1.05 x 10(-5) M) in a competitive manner . Furthermore, dactinomycin caused a parallel rightward shift of the concentration-response curve for the contractions in the rat colon induced by the NK-2 receptor agonist {Nle10}-NKA(4-10) . A selective inhibition of NK-2 receptors by dactinomycin was supported by the absence of inhibition of NK-1 receptors activation in guinea pig vas deferens and of NK-3 receptors in rat portal vein . The structural similarity of the cyclic peptide moieties of dactinomycin to L-659,877, a known NK-2 receptor antagonist, can probably account for the present observations.

FEBS Lett, 1991 Nov 4, 292(1-2), 232 - 6
Kirromycin-induced modifications facilitate the separation of EF-Tu species and reveal intermolecular interactions; Anborgh PH et al.; A simplified method for the separation of a kirromycin-sensitive tufB-encoded elongation factor Tu (EF-TuBs) from a kirromycin-resistant tufA product (EF-TuAr) was obtained by exploiting the specific increase of negative {corrected} charges induced by the antibiotic, resulting in a retarded elution of kirromycin-bound EF-TuBs on ionic chromatography . The kirromycin-free EF-TuBs is active in poly(Phe) synthesis and shows similar properties to EF-TuAsBs . As expected for these two distinct species, the dissociation of the EF-TuArBs.GTP complex in the presence of kirromycin shows a biphasic curve; in contrast, a monophasic GTP dissociation rate was found for a combination of two mutated EF-Tu species, EF-TuArBo, revealing the existence of intermolecular interactions . These observations prove for the first time the existence of cooperative phenomena between EF-Tu species in vitro, as suggested earlier by in vivo experiments.

South Med J, 1991 Nov, 84(11), 1396 - 8
Suppurative pylephlebitis; Drabick JJ et al.; Suppurative pylephlebitis is an unusual disease with an associated high mortality . Most cases are a complication of an intra-abdominal septic focus, but some may occur de novo . In the case we have presented, the diagnosis was made by modern imaging techniques that showed thrombus predominantly within the upper portal venous system . We hypothesize that the portal system was seeded through a gastric ulcer . The patient recovered completely with prolonged antibiotic therapy.

South Med J, 1991 Nov, 84(11), 1391 - 3
Mycobacterium fortuitum pulmonary infection complicating achalasia; Howard RS 2nd et al.; Achalasia is a cause of chronic aspiration pneumonia that may be complicated by pulmonary infection with Mycobacterium fortuitum . In any patient with achalasia, the presence of a pulmonary infiltrate that does not respond to routine antibiotic therapy should suggest the possibility of M fortuitum pulmonary infection, and sputum should be cultured for these organisms.

J Bacteriol, 1991 Nov, 173(21), 7004 - 11
A novel, highly efficient gene-cloning system for Micromonospora strains; Hasegawa M et al.; A highly efficient gene-cloning system for Micromonospora olivasterospora, a producer of the antibiotic fortimicin A (astromicin), suited to shotgun cloning has been developed . The system is supported by two new advancements accomplished in this study . One is the construction of novel plasmid vectors pMO116, pMO126, pMO133, pMO136, and pMO217, all consisting of replicons from newly found Micromonospora plasmids and selectable markers cloned from a neomycin-producing Micromonospora strain . The other advancement is the establishment of a new protocol for bacterial protoplasting in which some kinds of sugar alcohols are added in precultures . Such sugar alcohols were found to sensitize a wide taxonomical range of bacteria to lysozyme . The system is reproducible and reliable and has a high efficiency of more than 10(6) CFU/micrograms of DNA.

Infect Immun, 1991 Nov, 59(11), 3863 - 8
Deletion of the BCSP31 gene of Brucella abortus by replacement; Halling SM et al.; The 31-kDa salt-extractable immunogenic protein, BCSP31, was deleted from several Brucella abortus strains by replacement with a marker gene encoding resistance to the antibiotics kanamycin and neomycin . The BCSP31 gene replacement plasmids, constructed with ColE1-derived vectors, were introduced by electroporation into B . abortus strain 19 (S19), into a rough variant of B . abortus S19, and into B . abortus S2308, and antibiotic-resistant transformants were isolated . B . abortus S19 is an attenuated strain used as a vaccine for prevention of bovine brucellosis in the United States, and B . abortus S2308 is a commonly used challenge strain . The antibiotic-resistant isolates were all obtained by recombination; none were spontaneous mutants . Loss of the gene encoding BCSP31 and presence of the marker gene were confirmed by Southern analysis . Vector sequences were either absent or linked to the genome, indicating that ColE1-derived plasmids are not maintained in B . abortus . Survival of B . abortus mutant strains in the macrophagelike cell line J774 and in HeLa cells was examined and shown to be indistinguishable from that of the parental strain.

Clin Exp Immunol, 1991 Nov, 86(2), 304 - 10
Actinomycin D upregulates lipopolysaccharide induction of macrophage procoagulant expression and tumour necrosis factor-alpha production; Wheeler HR et al.; The antitumour antibiotic actinomycin D (Act D) and the aminosugar D-galactosamine both enhance the sensitivity of animals to bacterial lipopolysaccharide (LPS) . Lipopolysaccharide stimulates macrophage membrane-bound procoagulant activity (MPCA) and tumour necrosis factor-alpha (TNF-alpha) production in vitro . We investigated the effects of LPS combined with either Act D or D-galactosamine on procoagulant and TNF-alpha production in vitro . Actinomycin D directly induced procoagulant on the malignant monocytoid cell line WEHI 265, and synergized with LPS to enhance MPCA on both WEHI 265 cells and thioglycollate-induced peritoneal exudate macrophages . In the presence of Act D, exudate macrophages expressed procoagulant in response to concentrations of LPS 100,000-fold lower than normally required . Pulsing experiments demonstrated that LPS primed these cells within 4 h to respond to Act D, whereas 4 h priming with Act D inhibited subsequent procoagulant induction by LPS . Although its effects on TNF-alpha production were less intense, low levels of Act D more than doubled TNF-alpha produced by LPS-stimulated exudate macrophages . Procoagulant expression and TNF-alpha production were not always co-ordinately expressed; interferon-gamma (IFN-gamma) synergized with LPS to enhance both responses but when IFN-gamma was combined with Act D only procoagulant was upregulated . D-galactosamine failed to affect these macrophage responses . Results indicate different in vivo mechanisms of enhancement of LPS toxicity by these two agents.

J Gen Microbiol, 1991 Nov, 137 ( Pt 11), 2627 - 30
Identification of a sterol mutant of Neurospora crassa deficient in delta 14,15-reductase activity; Ellis SW et al.; A mutant (erg-3) of Neurospora crassa resistant to the polyene antibiotic nystatin was compared with its sensitive, wild-type parent to detect differences in sterol composition using gas chromatography-mass spectrometry . The major sterol in wild-type mycelia, comprising 80% of the total, was ergosterol . The major sterols in mutant mycelia, comprising 86% of the total, were delta 8,14-sterols . It is proposed that the nystatin-resistant strain is unable to synthesize ergosterol because it lacks delta 14,15-reductase activity as a result of a mutation in the erg-3 gene.

Zhonghua Wai Ke Za Zhi, 1991 Nov, 29(11), 687 - 8, 718
{Intraprostatic injection of azactam for chronic prostatitis}; Feng YP; Seventy-five cases of chronic prostatitis were treated with intraprostatic injection of azactam via transperineal route . Direct intraprostatic antibiotic injection was advantageous . The drug can cross the barrier of the lipoprotein epithelial membrane of the prostate with a high concentration in the gland and longer effects . Of the 75 patients, 73 (97.3%) were cured . The pharmacological properties of azactam are also described.

Food Addit Contam, 1991 Nov-Dec, 8(6), 737 - 48
Separation, identification and determination of lumichrome in swine feed and kidney; Kindack DG et al.; During surveillance of hog carcasses from Manitoba for antibiotic residues by the Health of Animals Laboratory, Agriculture Canada, Saskatoon, an unknown substance was found which produced tetracycline-like results with the methods used . This same substance was found in an implicated swine feed premix . Using various HPLC systems and columns, UV spectroscopy, reverse-phase TLC, and mass spectrometry, the substance was isolated from the feed premix, and identified as lumichrome, a photodegradation product of riboflavin . Traces of the same substance were found in riboflavin standard . Analysis of swine kidney, previously found to contain the unknown, showed the same substance was present at a level of about 1 ppm.

Biull Eksp Biol Med, 1991 Nov, 112(11), 523 - 5
{The antitumor activity of liposomal aclarubicin in vitro and in vivo}; Viadro MM et al.; Study on antitumor activity of free and liposomal anthracycline antibiotic aclarubicin in vitro and in vivo showed that liposomal aclarubicin was characterised by activity against ascitic Ehrlich carcinoma comparable to that of free aclarubicin when used in a dose of 25 mg/kg . Liposomal antibiotic had a more pronounced antimetastatic action and showed no toxicity (in a dose of 30 mg/kg) . Liposomal aclarubicin had a higher activating capacity with respect to the macrophage tumoricidal properties.

Drug Des Discov, 1991 Nov, 8(1), 57 - 67
Lipophilic N-acylpyrazinamide derivatives: synthesis, physicochemical characterization, liposome incorporation, and in vitro activity against Mycobacterium avium-intracellulare; Liu ZZ et al.; N-acetyl-(2), N-caproyl-(3), N-capryl-(4) and N-palmitoyl-pyrazinamide (5) were synthesized by reacting pyrazinamide (1) with acetic anhydride to prepare (2), or by reacting (1) in chloroform with the corresponding acid chlorides to prepare (3-5) . Products were identified by high resolution mass spectroscopy, elemental analysis, and 1H NMR . Melting points, enthalpies of fusion, solubility and octanol-water partition coefficients were determined . Hydrolysis of (2) indicated a pseudo first-order, pH-dependent degradation reaction . Apparent half life times of degradation ranged from 74.2 hours at pH 3 to 5.4 hours at pH 7.34 . Derivative (5) was incorporated in liposomes consisting of soy phosphatidylcholine and dipalmitoylphosphatidylglycerol (7:3 molar ratio) . The in vitro susceptibility of Mycobacterium avium-intracellulare (MAI) to the liposomal compound containing (5) was tested . MAI was susceptible to (5) at concentrations of 12.5-25 micrograms/ml, although MAI is not susceptible to the parent drug (1) . Thus, a new class of antimycobacterial agents with physicochemical properties suitable for stable incorporation within liposomes and high antibiotic efficacy against MAI is presented.

Phlebologie, 1991 Nov-Dec, 44(4), 865 - 71
{An unusual complication of ambulatory phlebectomy . Talc granuloma}; Ramelet AA; A review of the literature concerning the complications of ambulatory phlebectomy using the Muller technique . Description of a complication as yet unreported, silicotic granuloma, of which the author has seen 2 cases following the inappropriate use of antibiotic powder at the end of the operation . The prevention of this benign complication, as unnecessary as it is unesthetic, involves limiting the size of incisions and avoidance of the application of medicinal powder to a surgical wound.

Mol Plant Microbe Interact, 1991 Nov-Dec, 4(6), 602 - 7
Transformation of the oomycete pathogen, Phytophthora infestans; Judelson HS et al.; A stable transformation procedure has been developed for Phytophthora infestans, an oomycete fungus that causes the late blight diseases of potato and tomato . This is the first description of reliable methods for transformation in an oomycete pathogen . Drug-resistant transformants were obtained by using vectors that contained bacterial genes for resistance to hygromycin B or G418 fused to promoters and terminators from the Hsp70 and Ham34 genes of the oomycete, Bremia lactucae . Using polyethylene glycol and CaCl2, vector DNA was introduced into protoplasts as a complex with cationic liposomes or with carrier DNA only . Transformants were obtained at similar frequencies with each combination of promoter and selectable marker and were confirmed by DNA and RNA hybridization and phosphotransferase assays . Transformation occurred through the integration of single or tandemly repeated copies of the plasmids into genomic DNA, conferring mitotically stable drug-resistant phenotypes . The sizes of the marker gene mRNAs in each transformant and the results of transcript mapping studies were consistent with the function of the B . lactucae regulatory sequences in P . infestans . A hygromycin-resistant transformant was tested and found to maintain pathogenicity, indicating that the gene transfer procedure will be useful for the molecular analysis of genes relevant to disease.

Antimicrob Agents Chemother, 1991 Nov, 35(11), 2382 - 7
Isepamicin disposition in subjects with various degrees of renal function; Halstenson CE et al.; The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function . The subjects were divided into five groups: those with normal renal function (creatinine clearance {CLCR}, greater than 80 ml/min/1.73 m2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, less than 5 ml/min/1.73 m2) . Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period . The volumes of distribution of isepamicin were not significantly different among the five groups of patients . The total body clearance (CLP) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased . The CLP of isepamicin and CLCR were significantly related {(COP = 0.391.{CLCR} + 1.83; r2 = 0.878)} . Nonrenal clearance of isepamicin did not differ between groups . Hemodialysis augmented the CLP of isepamicin by approximately 25-fold . The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered . The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h . Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis . These data indicate that dosage adjustments are necessary in subjects with decreased renal function.

Trans R Soc Trop Med Hyg, 1991 Nov-Dec, 85(6), 793 - 5
Factors reducing mortality in typhoid ileal perforation; Kurlberg G et al.; A retrospective study of 42 patients treated surgically for typhoid ileal perforation found the mortality to be 24% . The study suggested that general peritonitis was the main cause of death in typhoid ileal perforation . However, the high mortality was significantly improved by adequate preoperative rehydration . The combination of chloramphenicol/gentamicin/metronidazole was superior to other antibiotic regimes . No mortality was recorded with this triple drug therapy.

Antibiot Khimioter, 1991 Nov, 36(11), 9 - 11
{Determination of nystatin component composition using HPLC and TLC with densitometry}; Mitrofanova VG et al.; The component composition of nystatin produced by an improved strain of Streptomyces noursei was determined by HPLC on Milichrom chromatograph (USSR) . It was shown that the antibiotic consisted of nystatins A1, A2, A3 and B and admixture substances . The data appeared to be in good agreement with the results of the complex TLC investigation, by using densitometry . The component composition of the samples was evidenced by SIEAP mass spectrometry . Physiochemical and biological characteristics of separate components are presented.

Paraplegia, 1991 Nov, 29(9), 628 - 31
Non-granulomatous spinal epidural abscess: a rehabilitation perspective; Weingarden SI et al.; Spinal epidural abscess (SEA) as a cause of back pain, fever, and neurological deficits has been recognised . Reports of this entity have increased in recent years, possibly likely secondary to increasing intravenous drug abuse . Most patients recover without neurological sequelae . Recent reports in fact indicate that those with persistent deficit have a much poorer prognosis for survival . As a result, few patients with SEA are seen in spinal injury rehabilitation programmes . Our 5 years experience with SEA was reviewed . Thirteen patients were admitted with residual neurological deficits following a course of prolonged antibiotic therapy . Of these most had progressive neurological improvement with only 3 of 4 remaining Frankel class A and 3 of 7 Frankel class C . The only mortalities (2) were secondary to the underlying medical problems . Most patients were discharged home.

Klin Monatsbl Augenheilkd, 1991 Nov, 199(5), 359 - 61
{Histiocytosis X (eosinophilic granuloma) of the caruncle}; Stanowsky A et al.; The lacrimal caruncle of an 11-year-old female patient developed a 2 mm x 3 mm-sized growth with the primary appearance of an abscess . The process did not regress under local antibiotic therapy and was excised . Histological examination revealed histiocytosis X (eosinophilic granuloma).

Monatsschr Kinderheilkd, 1991 Nov, 139(11), 759 - 64
{Lyme arthritis in childhood: monarthritis of the knee joint, clinically indistinguishable from monarthritis of unknown origin}; Huppertz HI et al.; Four children with monarthritis of the knee had no further manifestations of Lyme borreliosis, but a positive antibody titer against Borrelia burgdorferi as measured by Elisa . About 3 years after antibiotic therapy none of the children had arthritis, but one suffered from fibromyalgia and another child had still a vigorous reactivity against Borrelia burgdorferi antigens by Elisa and immunoblot . In this study 4 out of 20 children with recently recognized arthritis had Lyme arthritis which makes it a rather frequent disease . The clinical presentation could not distinguish these 4 children from 4 other children with monarthritis of the knee of unknown origin . In the absence of better diagnostic criteria, the association of monarthritis, not otherwise explained, with a positive Lyme serology seems to be sufficient evidence to establish a diagnosis of Lyme arthritis . After confirmation of the diagnosis children should be treated without delay.

J Microsc, 1991 Nov, 164 ( Pt 2), 95 - 106
Electron energy-loss spectroscopy analysis of adriamycin-plasma membrane interaction; Diociaiuti M et al.; Our previous studies on the mechanism of cytotoxic action of the anti-tumour drug adriamycin (ADR) indicated that this anthracyclinic antibiotic strongly modified the molecular architecture of the plasma membrane of human erythrocytes, presumably becoming incorporated within both lipid layers . In order to verify this hypothesis, electron energy-loss spectroscopy (EELS) has been used to compare the P content in control and ADR-treated erythrocyte ghosts . EELS measurements allowed us to reveal a significant reduction in the P/C ratio in erythrocyte ghosts after ADR treatment . This finding seems to reflect a phospholipid 'dilution' produced by the incorporation of the drug molecules in the membrane layers . A structural model of the ADR-membrane interaction is proposed.

Int J Colorectal Dis, 1991 Nov, 6(4), 214 - 6
Strictureplasty for ileo-colic anastomotic strictures in Crohn's disease; Sharif H et al.; We report an audit of outcome on 24 patients (16 females) who had a strictureplasty to treat ileo-colic anastomotic strictures . All except one patient had their original resection for Crohn's disease, and required reoperation because of symptoms of recurrent intestinal obstruction for a mean 9.3 months (range 1-36); the remaining patient was discovered to have ileo-colic anastomotic stricture before he underwent laparotomy for closure of loop ileostomy . At operation, four patients needed additional small bowel strictureplasties, two of whom also underwent small bowel resection for separate areas of phlegmonous disease . There was no post-operative mortality, three patients developed wound infection and one had a pelvic abscess, which settled on antibiotic therapy . Two patients have since died of unrelated disease . Five patients have since needed reoperation for recurrence; only one had a stricture at the site of previous strictureplasty . Over a mean follow-up of 70.8 months (range 18-393) all 22 living patients now have complete relief of symptoms.

Vet Clin North Am Small Anim Pract, 1991 Nov, 21(6), 1299 - 306
Pet avian medicine . Case reports; Oglesbee BL; Four case reports are presented . The first involves chronic lead toxicity in a Yellow-naped Amazon Parrot, which presented for a shoulder injury . The second discusses Aspergillosis in an African Grey Parrot following smoke inhalation and systemic antibiotic use . The third describes Chlamydiosis in a recently imported Amazon Parrot, and the final case concerns rhinitis/sinusitis in a cockatiel.

Optom Vis Sci, 1991 Nov, 68(11), 853 - 7
Corneal immune ring as a complication of soft extended wear contact lens use; Klein P; Corneal immune ring (CIR) appeared in the eyes of three patients who wore their extended wear contact lenses while sleeping . CIR's have not been reported as a complication associated with the wear of soft extended wear lenses . The CIR appeared within days of an episode of ulcerative keratitis with an infiltrative component . Treatment with topical antibiotic and anti-inflammatory agents produced resolution of the corneal lesions . The clinical appearance of the lesions as well as the time frame involved suggest that the immune response that produced the CIR was triggered by bacterial endotoxin through the properdin-mediated complement pathway.

Oncol Nurs Forum, 1991 Nov-Dec, 18(8), 1349 - 56
A comparison of transparent adherent and dry sterile gauze dressings for long-term central catheters in patients undergoing bone marrow transplant; Shivnan JC et al.; Patients undergoing bone marrow transplant (BMT) are at great risk of infection and sepsis . Long-term central catheters (LTCCs), required for IV therapy, can be a portal of entry for infectious agents . This randomized, prospective study compared two types of catheter dressings in 98 patients undergoing BMT: a dry sterile gauze dressing (DSGD) changed daily and a transparent adherent dressing (TAD) changed every four days . Study outcomes included incidence and severity of local and systemic complications, patient assessment of comfort, and calculation of nursing time . One case of catheter-related infection occurred during the study . No significant differences existed between the two dressings in the incidence of positive skin cultures or local complications with the exception of skin irritation . The TAD caused less skin irritation, was preferred by patients, cost less, and required less nursing time . The findings indicate that TADs provide a safe, comfortable, and cost-effective alternative to DSGDs for patients undergoing BMT and receiving antibiotic support during aplasia.

J Pediatr Ophthalmol Strabismus, 1991 Nov-Dec, 28(6), 341 - 3
Treatment of acute dacryocystitis in neonates; Pollard ZF; Twenty-five newborns with acute dacryocystitis underwent probing of the nasolacrimal duct . All had a resolution of the acute dacryocystitis . Only one continued to have epiphora and had to undergo a subsequent probing with silicone intubation at 9 months of age . All were probed without anesthesia, being mummified and held by nurses while the author performed the probing . Only five were treated with parenteral and topical antibiotics for a week prior to probing while 20 were probed without any prior antibiotic therapy . Additionally, five of six mucoceles of the lacrimal sac which did not resolve in the 1st 2 weeks of life with massage were successfully probed without anesthesia . Four of the five mucoceles had developed an acute dacryocystitis on conservative management . Probing of the nasolacrimal duct in the newborn period is a safe and successful approach for acute dacryocystitis . It is a highly successful procedure for the treatment of acute dacryocystitis with a very low morbidity rate.

J Dermatol Surg Oncol, 1991 Nov, 17(11), 862 - 4
Chondrodermatitis nodularis chronica helicis . Successful treatment with the carbon dioxide laser; Taylor MB; Chondrodermatitis nodularis chronica helicis is a painful, persistent, or recurrent inflammatory lesion involving the cartilage and skin of the external ear . These lesions are resistant to many therapeutic modalities and often recur even after surgical excision . The CO2 laser was used to vaporize the cutaneous nodules and involved cartilage . The wounds were allowed to heal with only minimal care using hydrogen peroxide cleansing and applications of topical antibiotic ointment . Twelve lesions have been treated with no recurrences after 2 to 15 months . There have been no complications or infections following laser surgery . The pain from these lesions is gone immediately following laser surgery . Healing with excellent cosmetic results is complete usually within 3 to 4 weeks.

Otolaryngol Head Neck Surg, 1991 Nov, 105(5), 717 - 22
The Caldwell-Luc procedure in 1991; Blitzer A et al.; In the pre-antibiotic era, George Caldwell and Guy Luc both designed an operation to remove infected polypoid tissue from the maxillary antrum, as well as to provide drainage and ventilation of the sinus . With the development of antibiotics and the surgical endoscopes, many of the former indications for the Caldwell-Luc procedure have changed . However, the Caldwell-Luc procedure still offers optimal exposure for decompression of Grave's ophthalmopathy, pterygomaxillary space surgery, management of some maxillary trauma, removal of antral foreign bodies, repair of some oral-antral fistulae, management of maxillary osteomyelitis and benign maxillary tumors, and irreversible mucosal disease and endoscopic surgical failures.

J Cardiovasc Surg (Torino), 1991 Nov-Dec, 32(6), 800 - 6
Bioprosthetic valve endocarditis: factors affecting bad outcome; Gagliardi C et al.; Prosthetic valve endocarditis (PVE) remains an uncommon but serious complication of cardiac valve replacement . We analysed several risk factors (active or healed, early or late endocarditis, congestive heart failure, arterial emboli etc.) in order to identify the factors which may predict bad outcome . The overall mortality rate was 46.8% (15/32 patients) . There was a significantly higher mortality rate in patients with early endocarditis (80%) than in those with late endocarditis (38%) (p less than 0.01) . In the group of patients who underwent reoperation, the mortality rate was higher in those with active endocarditis (70%) than in those with healed endocarditis (28.5%) (p less than 0.05) . We believe that combined medical and surgical treatment is the best management for bioprosthetic valve endocarditis, with the institution of appropriate preoperative antibiotic therapy, to attempt to achieve sterilization.

J Anim Sci, 1991 Nov, 69(11), 4563 - 9
Suppression of sheep and goat lymphocyte proliferation by sheep, goat, and sheep x goat hybrid trophoblast tissue cultures; Roth TL et al.; Immunosuppressive activity of conditioned medium from cultured ovine, caprine, and hybrid trophoblast tissue was examined . Conceptuses were obtained from naturally mated donor ewes and does at d 20 of gestation and trophoblast tissue was cultured for 24 h in medium supplemented with 15% calf serum and 1% antibiotic/antimycotic . Conditioned medium was added to pokeweed mitogen-stimulated sheep and goat lymphocyte cultures . Quantification of {3H}thymidine uptake by cells was used to measure lymphocyte proliferation . Ovine, caprine, and hybrid conditioned medium effectively suppressed sheep and goat lymphocyte proliferation (P less than .01) . There were no differences (P greater than .05) between the immunosuppressive activity of the three tissue types on either sheep or goat lymphocytes . For all treatment groups, sheep lymphocytes were suppressed more than goat lymphocytes (P less than .05) . These results indicate that, at d 20 of gestation, sheep x goat hybrid trophoblast tissue is capable of suppressing pokeweed mitogen-stimulated lymphocyte proliferation.

Oncogene, 1991 Nov, 6(11), 1983 - 9
Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines; Garcia R et al.; The effect of herbimycin A, an ansamycin antibiotic which inhibits cellular transformation by retroviral tyrosine kinases, on the monolayer growth of seven colon tumor cell lines and one cell line established from normal colonic mucosa, CCL239, was examined . Each colon tumor cell line tested showed dose-dependent growth inhibition in response to herbimycin A . A 125ng ml-1 dose of the antibiotic caused greater than 40% growth inhibition in all colon tumor cell lines after two cell doublings . In contrast, at similar herbimycin A concentrations only 12% inhibition was observed in 'normal' CCL239 cells . No major morphologic changes were observed at the light microscopic level in any of the tumor cell lines or CCL239 cells in response to treatment with herbimycin A . Studies using the HT29 colon adenocarcinoma cell line showed dose-dependent inactivation of pp60c-src by herbimycin A, resulting in decreased autophosphorylation, enolase phosphorylation and steady-state levels, which correlated with cellular growth inhibition . Herbimycin A-induced reductions in pp60c-src kinase activity preceded changes in pp60c-src steady-state levels . Growth and pp60c-src inhibition were reversible following removal of herbimycin A from cell culture media . Our results suggest that regulation of pp60c-src tyrosine kinase activity may be important in growth control of colon tumor cells.

Head Neck, 1991 Nov-Dec, 13(6), 531 - 9
Mediastinal and thoracic complications of necrotizing fasciitis of the head and neck; Lalwani AK et al.; Mediastinal and thoracic extension of head and neck infections are rare but occur even in the modern antibiotic era . Early intervention is paramount to successful clinical outcome . 111Indium-labeled white blood cell (WBC) scan, a new imaging modality, appears to play a role in complementing computed tomographic (CT) findings, demonstrating early extension of disease, and following therapeutic efficacy . Together, the CT scan and WBC scan aid in directing early intervention and extent of surgery in this disease of high-potential mortality . We report 3 cases of deep head and neck infection complicated by mediastinal extension, including mediastinitis, pericardial effusion, and tamponade, empyema, and respiratory failure . Early surgical intervention included neck drainage, tracheostomy, thoracotomy, and pericardiotomy . While usually associated with greater than 50% mortality, all of the patients in this series survived . Based on our experience, we recommend prompt aggressive surgical debridement in treating mediastinal complications resulting from head and neck infections.

J Hosp Infect, 1991 Nov, 19(3), 167 - 74
Bacterial contamination of air and surgical wounds during joint replacement operations . Comparison of two different types of staff clothing; Scheibel JH et al.; Compared with conventional surgical clothing, polypropylene coveralls reduced the bacterial contamination of the air of a conventionally ventilated operating room by 62% . The contamination of surgical wounds during joint replacement was also reduced, but not to a significant degree . Sixteen percent of the bacteria sampled from the wounds were resistant to the prophylactic antibiotic and the importance of a clean air system for performing joint replacement operations is stressed . The use of commercially available non-woven swabs for sampling bacteria from the surgical wound compared favourably with the use of specially prepared velvet pads.

Neuropharmacology, 1991 Nov, 30(11), 1167 - 71
Actions of D-cycloserine at the N-methyl-D-aspartate-associated glycine receptor site in vivo; Emmett MR et al.; The antibiotic, D-cycloserine has been shown to be a partial agonist at the N-methyl-D-aspartate (NMDA)-coupled, strychnine-insensitive glycine receptor by in vitro receptor binding . This partial agonism was further investigated in an in vivo system, by monitoring changes in levels of cyclic guanosine-monophosphate (cGMP), a well characterized second messenger response, mediated by the NMDA receptor complex, in the cerebellum of the mouse . Parenteral injections of D-cycloserine produced a biphasic dose-response curve which suggested partial agonism . In support of this contention, when intracerebellar injections were made together with D-serine, a glycine agonist, D-cycloserine attenuated the N-methyl-D-aspartate receptor-mediated increase in levels of cGMP . Likewise, systemic administration of D-cycloserine attenuated increases in cGMP induced by pentylenetetrazol . These data are relevant to the study of N-methyl-D-aspartate-mediated neurotransmission, since D-cycloserine is a parenterally bioavailable compound, with both agonist and depressant properties at the N-methyl-D-aspartate-associated glycine receptor.

Mol Pharmacol, 1991 Nov, 40(5), 790 - 7
Trichosporin-B-III, an alpha-aminoisobutyric acid-containing peptide, causes Ca(2+)-dependent catecholamine secretion from adrenal medullary chromaffin cells; Tachikawa E et al.; We examined the effect of trichosporin-B-III, an alpha-aminoisobutyric acid-containing antibiotic peptide consisting of 19 amino acid residues and a phenylalaninol, on catecholamine secretion from cultured bovine adrenal chromaffin cells . Incubation of the cells with trichosporin-B-III (3-20 microM) caused an increase in the secretion of catecholamines . The secretion induced by trichosporin-B-III at low concentrations (3 and 5 microM) was completely dependent on external Ca2+, whereas that induced by higher concentrations (10 and 20 microM) was partly independent of Ca2+ . Trichosporin-B-III at low concentration (5 microM) did not increase the release of lactate dehydrogenase, a marker enzyme of cytoplasm, from the cells . In contrast, the peptide at higher concentration (10 microM) increased the release of the enzyme . Trichosporin-B-III also caused both 45Ca2+ influx into the cells and an increase in the intracellular free Ca2+ concentration . The increases in catecholamine secretion and 45Ca2+ influx behaved similarly in relation to trichosporin-B-III concentration (3-10 microM) . The time courses of the increases in secretion, 45Ca2+ influx, and intracellular free Ca2+ concentration induced by trichosporin-B-III were also quite similar . Trichosporin-B-III-induced (at 5 microM) secretion was not affected by the elimination of Na+ from the incubation medium or by the addition of tetrodotoxin, a blocker of highly selective voltage-dependent Na+ channels, or hexamethonium, a blocker of nicotinic acetylcholine receptors . On the other hand, both diltiazem (2-200 microM) and nicardipine (1-200 microM), blockers of voltage-dependent Ca2+ channels, inhibited the secretion induced by trichosporin-B-III (5 microM) in a concentration-dependent manner . Trichosporin-B-III-induced (at 5 microM) secretion also was suppressed by the addition of Mn2+ (5 mM) to the medium . The diltiazem (20 microM) inhibition of trichosporin-B-III-induced (at 5 microM) secretion was reversed by increasing the external Ca2+ concentration . These results indicate that trichosporin-B-III causes the secretion of catecholamines from bovine adrenal chromaffin cells by two mechanisms, Ca2+ dependent and Ca2+ independent (only at high concentrations of trichosporin-B-III) . Furthermore, these results strongly suggest that trichosporin-B-III, in Ca(2+)-dependent secretion, activates endogenous voltage-dependent Ca2+ channels, or itself forms the channels in the membranes, and induces Ca2+ influx into the cells.

J Bacteriol, 1991 Nov, 173(21), 7018 - 20
A hisT::Tn5 mutation affects production of microcins B17, C7, and H47 and colicin V; Rodriguez-Sainz MC et al.; A Tn5 insertion decreasing the production of microcin B17 was mapped to 50.2 min on the Escherichia coli chromosome map . Sequence analysis showed that the insertion disrupted hisT, the gene encoding pseudouridine synthase I, a tRNA-modifying enzyme . hisT::Tn5 mutant cells were also shown to be defective for the production of other antibiotic peptides, such as microcin C7, microcin H47, and colicin V.

Proc Natl Acad Sci U S A, 1991 Oct 15, 88(20), 8963 - 6
Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism: deformylation with olefin formation; Roberts ES et al.; As we have briefly described elsewhere, cytochrome P-450 catalyzes the oxidative deformylation of cyclohexane carboxaldehyde to yield cyclohexene and formic acid in a reaction believed to involve a peroxyhemiacetal-like adduct formed between the substrate and molecular oxygen-derived hydrogen peroxide . This reaction is a useful model for the demethylation reactions catalyzed by the steroidogenic P-450s, aromatase, and lanosterol demethylase . In the present study, the cytochrome P-450-catalyzed formation of olefinic products from a series of xenobiotic aldehydes has been demonstrated . Isobutyraldehyde and trimethylacetaldehyde, but not propionaldehyde, are converted to the predicted olefinic products, suggesting a requirement for branching at the alpha carbon . In addition, the four C5 aldehydes of similar hydrophobicity were compared for their ability to undergo the reaction . The straight-chain valeraldehyde gave no olefinic products with five different rabbit liver microsomal P-450 isozymes . However, increasing activity was seen with the other isomers in the order of isovaleraldehyde, 2-methylbutyraldehyde, and trimethylacetaldehyde, with all of the P-450 cytochromes . The catalytic rate with trimethylacetaldehyde is highest with antibiotic-inducible P-450 form 3A6, followed by phenobarbital-inducible form 2B4 and ethanol-inducible form 2E1 . Citronellal, a beta-branched aldehyde that is found in many essential oils and is widely used as an odorant and a flavorant, was found to undergo the oxidative deformylation reaction to yield 2,6-dimethyl-1,5-heptadiene, but only with P-450 2B4 . The oxidative cleavage reaction with olefin formation appears to be widespread, as judged by the variety of aldehydes that serve as substrates and of P-450 cytochromes that serve as catalysts.

CMAJ, 1991 Oct 15, 145(8), 953 - 61
Chlamydia trachomatis cervical infection: prevalence and determinants among women presenting for routine gynecologic examination; Masse R et al.; OBJECTIVE: To determine the prevalence of and risk indicators for Chlamydia trachomatis cervical infection among women presenting for a periodic medical examination . DESIGN: Prevalence study . SETTING: Centre local de services communautaires (CLSC) Saint-Louis du Parc, Montreal . PATIENTS: All women presenting for a routine gynecologic examination from May 1985 to July 1986 . Of the 773 (99%) who agreed to participate 56 were excluded because of inadequate diagnostic tests (34), antibiotic intake in the preceding 6 weeks (19) or loss to follow-up after the initial visit (3) . OUTCOME MEASURES: Culture was the diagnostic standard, but rapid diagnostic tests were also used . From the identified cases logistic regression analysis was used to evaluate the following risk indicators: age, place of residence, use of oral contraceptives, sexual partners and frequency, history of sexually transmitted disease (STD) and abnormalities found on genital examination . MAIN RESULTS: Fifty-one of the women were found to have C . trachomatis infection, for a prevalence rate of 7.1%; 32 (63%) were completely asymptomatic . Three independent indicators were found: age of 25 years or less (odds ratio {OR} 3.2, 95% confidence limits {CL} 1.8 and 5.9), cervical erythema, contact bleeding or mucopurulent exudate (OR 2.5, 95% CL 1.4 and 4.5) and residency in the CLSC area (OR 2.3, 95% CL 1.1 and 5.1) . A history of STD or vaginitis had a significant protective effect in women 30 years of age or more (OR 0.2) . CONCLUSIONS: Case-finding for chlamydial infection could be an effective public health measure among women 25 years of age or less and among those with signs of cervicitis when they present for a Papanicolaou test.

Biochim Biophys Acta, 1991 Oct 10, 1075(2), 141 - 5
The conformation of echinomycin in DMSO solution; Yu C et al.; The conformation of the antibiotic echinomycin in DMSO solution has been determined from two-dimensional NMR and distance geometry calculation with distance constraints . Five converged conformations were calculated with NOE distance constraints followed by restraint energy minimization.

Biochem Pharmacol, 1991 Oct 9, 42(9), 1673 - 81
Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives . Relationship to antioxidant activity and to iron ion-reducing ability; Laughton MJ et al.; We investigated the ability of various plant flavonoids (a) to inhibit 5-lipoxygenase and cyclooxygenase activities in rat peritoneal leukocytes, (b) to inhibit lipid peroxidation in rat liver microsomes, and (c) to stimulate DNA degradation caused by the antibiotic bleomycin in the presence of ferric ions . These compounds were compared with a range of synthetic phenolic substances including carnosol, vanillin, vitamin E and its analogue trolox c . The flavonoids were potent inhibitors of non-enzymatic peroxidation in membranes but this was not significantly correlated with their ability to inhibit either pathway of eicosanoid synthesis, suggesting that their mode of inhibition of 5-lipoxygenase/cyclooxygenase is not simply due to interception of peroxyl radicals generated at the active site of the enzymes . Many of the flavonoids and other compounds (including carnosol, vitamin E and trolox c) stimulated Fe3+/bleomycin-dependent DNA degradation . Those flavonoids which stimulated DNA degradation at low concentrations but which inhibited it at higher concentrations ("biphasic" effect, possibly caused by changing relative contributions of ability to reduce ferric-bleomycin or to chelate iron ions from the bleomycin) were selective inhibitors of 5-lipoxygenase compared to cyclo-oxygenase . In contrast, those flavonoids that did not stimulate DNA degradation at all proved to be cyclo-oxygenase selective inhibitors . Compounds that increased Fe3+/bleomycin-dependent DNA damage up to a maintained plateau were non-selective inhibitors of both 5-lipoxygenase and cyclo-oxygenase . Thus, a combination of iron-chelating and iron ion-reducing properties appears to be required for selective 5-lipoxygenase inhibition by phenolic compounds . Carnosol, vitamin E and trolox c were also found to be 5-lipoxygenase inhibitors of varying potency, and all were less active as cyclo-oxygenase inhibitors.

Biochem Pharmacol, 1991 Oct 9, 42(9), 1661 - 71
Specific inhibition of cytoplasmic protein tyrosine kinases by herbimycin A in vitro; Fukazawa H et al.; Herbimycin A is an antibiotic which reverses transformation caused by various src related oncogenes . The reversion of transformation is restricted to cells transformed by tyrosine kinase coding oncogenes, and accompanies a decrease in kinase activity of the oncogene products . We have shown in vitro that herbimycin A directly inactivates p60v-src kinase by conjugating with SH group(s) of the kinase, raising the possibility that the molecular target of the antibiotic for reversion of v-src transformation is the p60v-src itself . To investigate the relevance of its in vitro tyrosine kinase inactivating activity to in vivo transformation reversing activity, we examined the specificity of herbimycin A for inhibition of cAMP-dependent kinase, protein kinase C and p210bcr-abl tyrosine kinase in vitro . Herbimycin A had no inhibitory effect on the activities of cAMP-dependent kinase or protein kinase C, whereas the SH-reagent N-(9-acridinyl)maleimide, which inactivates p60v-crc in vitro by a mechanism similar to that of herbimycin A, blocked the two serine/threonine kinases . On the other hand, the activity of p210bcr-abl tyrosine kinase was inhibited by herbimycin A treatment . The results indicate that herbimycin A specifically binds to reactive SH group(s) of cytoplasmic protein tyrosine kinases, and confer the biochemical basis for its selectivity in reversing cell transformation.

J Biol Chem, 1991 Oct 5, 266(28), 18907 - 13
Degradation of the neuropeptide somatostatin by cultivated neuronal and glial cells; Lucius R et al.; The enzymatic degradation of the neuropeptide somatostatin was investigated in cultivated cells and subcellular fractions from rat brain . Dissociated neurones, astrocytes, and oligodendrocytes obtained from rat cerebral cortex were of more than 85-98% purity as evidenced by immunostaining with antisera to cell specific markers . All of these cell types were able to cleave radiolabeled somatostatin to smaller fragments, especially cultivated astrocytes with the highest specific activity . The neuroblastoma cell line N1E-115 did not measureably cleave somatostatin . The somatostatin-degrading proteases of the cultivated brain cells could be differentiated by their sensitivity to protease inhibitors and by the fragments produced: astrocytes contain a metallo-endoprotease sensitive to phenanthroline which cleaves somatostatin at the Phe6-Phe7 and Thr10-Phe11 bonds, whereas the endoprotease(s) of neurones and oligodendrocytes was insensitive to chelating agents but strongly inhibited by the antibiotic bacitracin . In accordance with this, the bacitracin-sensitive activity was mainly recovered in the synaptic plasma membrane and myelin subcellular fractions obtained by differential centrifugation of rat cerebral cortex homogenate . However, the highest total and specific somatostatin-degrading activity was detected in the cytosolic fraction.

J Otolaryngol, 1991 Oct, 20(5), 315 - 9
Iatrogenic subcutaneous cervicofacial and mediastinal emphysema; Rossiter JL et al.; Subcutaneous emphysema of the head, neck and mediastinum occurs with a variety of disease processes . Most cases involve the passive escape of air from the aerodigestive tract into subcutaneous tissues . The many causes include head and neck surgical procedures, tracheal and esophageal trauma, intraoral trauma, foreign bodies and neoplasms of the aerodigestive tract, and pulmonary barotrauma from mechanical ventilation or in patients with pulmonary disorders . Subcutaneous emphysema secondary to active injection of air has recently been reported following certain dental procedures . An interesting case of diffuse cervicofacial and mediastinal emphysema following a difficult extraction of an infected lower molar tooth with a high-pressure air drill is presented . The patient required airway observation and high-dose antibiotic therapy . Early recognition of this unique problem is essential in preventing such life-threatening complications as airway obstruction, mediastinitis, deep neck infection, and cardiac failure . Diagnostic and therapeutic recommendations are included.

Br J Surg, 1991 Oct, 78(10), 1185 - 6
Effective surgical treatment for mammary duct fistula; Dixon JM et al.; Forty-two patients with 43 mammary duct fistulae, including 23 with a history of at least one previous unsuccessful operation, were treated by excision of the involved duct and fistula alone (15 fistulae) or excision of the fistula combined with total duct excision (28 fistulae) . The wounds were closed primarily with antibiotic cover . Two patients had a minor wound infection which settled within 1 month of surgery; one patient developed superficial necrosis of the nipple and one patient required a second operation to excise a discharging sinus . No fistula recurrence has been identified after a median follow-up of 2.5 years . Excision of the involved duct and fistula alone, or excision of the fistula combined with total duct excision performed with antibiotic cover, is probably the treatment of choice for mammary duct fistula.

Eur J Haematol, 1991 Oct, 47(4), 246 - 52
Kinetics of transfused neutrophils in peripheral blood and BAL fluid of a patient with variant X-linked chronic granulomatous disease; Emmendorffer A et al.; Patients with chronic granulomatous disease (CGD), an uncommon inherited disorder of phagocytes resulting in the defective production of reactive oxygen intermediates, are prone to bacterial and fungal infections . In the case presented, therapeutic efforts including white cell transfusions, and amphotericin B and IFN gamma administration were undertaken to treat pneumonia caused by Aspergillus fumigatus . During a phase of artificial respiration, transfused white cells in peripheral blood and bronchoalveolar lavage fluid were monitored in order to examine their kinetics and functional activity . Using flowcytometrical methods, host-derived and transfused neutrophils could be distinguished by cytochrome b558 expression using the monoclonal antibody 7D5 for immunofluorescent staining as well as by production of reactive oxygen intermediates . Transfused PMN could be detected in both compartments and their kinetics could be followed up to 24 hours after transfusion . Using flowcytometry, even small numbers of transfused PMN could be measured during episodes of extreme leukocytosis . Since functionally intact transfused PMN were found in the bronchioalveolar lavage fluid, white cell transfusions in combination with antibiotic and immunomodulating therapy should be considered a part of the therapeutic regimens for life-threatening infections in CGD patients.

Arch Surg, 1991 Oct, 126(10), 1287 - 91
Decortication for childhood empyema . The primary provider's peccadillo; Kennedy AS et al.; Of the 31 children treated for empyema thoracis secondary to pneumonitis at the Loma Linda University Medical Center, Loma Linda, Calif, from 1980 to 1990, 23 responded to prompt directed antibiotic therapy coupled with drainage, usually tube thoracostomy . All patients were cured clinically; some demonstrated residual pleural reaction with chest roentgenography or computed tomography that resolved over time . Decortication was necessary in eight severely ill children; three required concurrent lung resection for abscess . Distinct from the nonoperated group, there was a pattern of initial antibiotic trials in these patients averaging 6.5 different drugs plus delayed drainage of effusions . Delay in the initiation of antibiotic therapy was six times longer for the operated vs the nonoperated group . Delay to tube thoracostomy was 18 days for the decorticated children compared with 5.4 days for the nondecorticated children . All eight children responded completely and rapidly to their decortications . Roentgenographic changes lagged considerably behind the clinical course of the child, and computed tomographic scans provided better identification of chest tube placement but little information predictive of the need for decortication . Decortication for empyema seldom is necessary when a child is treated promptly with appropriate antibiotics directed by thoracentesis findings, and drainage, usually tube thoracostomy . The criterion for decortication is persistent sepsis, not the roentgenographic appearance of the chest.

Ann Thorac Surg, 1991 Oct, 52(4), 861 - 2
Constrictive pericarditis from Nocardia asteroides infection; Kessler R et al.; Human nocardiosis usually involves the respiratory tract or the skin but may disseminate to virtually any organ . It occurs in immunocompromised hosts as well as individuals with no apparent predisposition . Involvement of the pericardium is uncommon, having been reported infrequently in the past, but mandates surgical management . This report describes the course of a patient with chronic constrictive pericarditis from nocardia successfully treated with pericardiectomy and appropriate antibiotic therapy.

Am Rev Respir Dis, 1991 Oct, 144(4), 909 - 13
Pulmonary surfactant as a vehicle for intratracheal delivery of technetium sulfur colloid and pentamidine in hamster lungs; Kharasch VS et al.; Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs . In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5) . Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline . After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base . Autoradiographs were examined to evaluate 99mTc distribution . The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02) . Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity . Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry . We calculated the fraction of each lung slice with detectable radioactivity . The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02) . The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity . There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47) . We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread.

Am J Ophthalmol, 1991 Oct, 112(4 Suppl), 10S - 14S
Current therapy for bacterial keratitis and bacterial conjunctivitis; Steinert RF; Therapy of bacterial keratitis and conjunctivitis requires that antibiotics be administered to eliminate viable bacteria . Only a limited number of ophthalmic antibiotics are commercially available . Although generally adequate for the treatment of bacterial conjunctivitis, the commercial preparations are believed to contain too low a concentration of antibiotic for the treatment of bacterial keratitis . Using products designed for parenteral administration, the ophthalmologist or the pharmacist formulates so-called fortified preparations containing much higher antibiotic concentrations . Because of their limited spectrum of action, two fortified preparations generally are administered concurrently . Topical application is the most effective route of antibiotic administration for treatment of bacterial keratitis . Antibiotics may also be injected periocularly, a method with risk, or intravenously, a method of uncertain efficacy.

South Med J, 1991 Oct, 84(10), 1188 - 91
Effect of anorexia nervosa on pulmonary immunocompetence; Tenholder MF et al.; Pulmonary infection due to opportunistic organisms and usually nonpathogenic mycobacteria may occur whenever immune defenses are weakened by external factors . These factors include neutropenia, treatment with corticosteroids or cytotoxic agents, previous antibiotic therapy, and nosocomial hazards (eg, catheters, ventilators) . Nutritional deprivation is also often implicated as an important coexistent variable . An infection due to Mycobacterium xenopi (usually a nonpathogenic mycobacterium) in a patient with anorexia nervosa and no other predisposing factor for infection provides a model for discussing the possible effects of malnutrition on pulmonary immunocompetence . Since pulmonary infection in anorexia nervosa is often subtle, early evaluation of depressed cell-mediated immunity is appropriate.

Proc Natl Acad Sci U S A, 1991 Oct 1, 88(19), 8835 - 9
Studies on DNA-cleaving agents: computer modeling analysis of the mechanism of activation and cleavage of dynemicin-oligonucleotide complexes; Wender PA et al.; Dynemicin A is a recently identified antitumor antibiotic . Upon activation, dynemicin is reported to cause double-stranded cleavage of DNA, putatively through the intermediacy of a diradical . Computer modeling of this activation and cleavage process is described herein as part of an effort to establish a structural hypothesis for this mechanistic sequence and for the design of simple analogues . Intercalation complexes of duplex dodecamers {d(CGCGAATTCGCG)}2 and {d(GC)6}2 with both enantiomers of dynemicin and of all related mechanistic intermediates are evaluated . Examination of these structures shows that cycloaromatization of dynemicin to a diradical intermediate results in the rotation of the diradical-forming subunit with respect to the intercalation plane that is of an opposite sense for the two dynemicin enantiomers . In addition, the activation of the (2S) enantiomer of dynemicin occurs by a less restricted approach trajectory than the corresponding (2R) enantiomer . In all complexes, the 5'-3' strand is at least 1 A closer than the 3'-5' strand to the diyl intermediate . As a result, complexes are produced in which the diyl moiety is aligned along {(2S)} or across {(2R)} the minor groove, leading to different predictions for the selectivity of radical-initiated, oxidative lesion of DNA . Molecular dynamics simulations are found to support these predictions, including the 3-base-pair offset cleavage reported for dynemicin.

Proc Natl Acad Sci U S A, 1991 Oct 1, 88(19), 8553 - 7
A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin; Guilfoile PG et al.; Sequence analysis of the drrAB locus from Streptomyces peucetius (American Type Culture Collection 29050) reveals the presence of two genes, drrA and drrB, both of which are required for daunorubicin and doxorubicin (Adriamycin) resistance in the heterologous host Streptomyces lividans . The DrrA protein is similar to a large family of ATP-binding transport proteins, including the proteins encoded by the mdr genes from mammalian tumor cells, which confer resistance to daunorubicin, doxorubicin, and some other structurally unrelated chemotherapeutic agents . The DrrB protein shows no significant similarity to other known proteins but is probably very hydrophobic, suggesting that it is located in the bacterial membrane . These two proteins may act jointly to confer daunorubicin and doxorubicin resistance by an analog of the antiport mechanism established for mammalian tumor cells that contain amplified or overexpressed mdr genes . Transcriptional analysis of the drrAB region supports the presence of one transcript containing drrA and drrB and indicates that these genes are expressed only during antibiotic production.

Postgrad Med, 1991 Oct, 90(5), 77 - 80, 83-6
Pneumonia and chronic obstructive pulmonary disease . What special considerations does this combination require?
Paz HI, Wood CA.
Patients with chronic obstructive pulmonary disease are at increased risk for both community- and hospital-acquired pneumonia, most often through aspiration . Community-acquired pneumonia often manifests with acute onset of chills, fever, cough, and pleuritic chest pain . Atypical pneumonia syndromes are characterized by subacute onset over several days and constitutional complaints . Hospital-acquired pneumonia may be contracted during altered consciousness or after intubation, ventilation, or exposure to pathogens . Knowledge of the disease process and the means to accurately diagnose these infections allows physicians to prescribe effective antibiotic therapy . Stable patients may receive oral therapy, but with severe or hospital-acquired pneumonia, parenteral therapy is required . Combinations of agents may be needed to cover the variety of pathogens that may be present.

Neurology, 1991 Oct, 41(10), 1571 - 82
Central nervous system abnormalities in Lyme neuroborreliosis; Halperin JJ et al.; Intrathecal production of anti-Borrelia burgdorferi antibody occurs frequently in CNS Lyme, yet reliable diagnosis of neuroborreliosis is still considered difficult and controversial . Therefore, we assessed the utility of this measurement in 103 Lyme patients . Among 15 patients with Lyme meningoradiculitis and 41 controls, diagnostic specificity was 93% and sensitivity 87% . Application of this method permits the identification of a rare B burgdorferi-associated multifocal encephalitis (brain infection) and its differentiation from a milder encephalopathy, or confusional state; the latter may not require CNS bacterial invasion . The encephalitis involves white matter more often than gray; severity varies widely . Of six patients with this antibiotic-responsive encephalitis, five were positive for HLA DQw3(DQw7) . We conclude that (1) measurement of intrathecal antibody production is a reliable indicator of CNS infection, (2) North American neuroborreliosis includes the same spectrum of neurologic dysfunction as described in Europe, and (3) HLA typing may be useful in furthering our understanding of severe CNS involvement.

Mayo Clin Proc, 1991 Oct, 66(10), 1041 - 5
Pyopneumopericardium attributed to an esophagopericardial fistula: report of a survivor and review of the literature; Miller WL et al.; Herein we describe a case of pyopneumopericardium that resulted from formation of an acquired esophagopericardial fistula in a patient with silent, benign esophageal ulcer disease . Atypical features on initial examination suggested congestive heart failure or a pneumonic process (or both) . The delayed development of pneumopericardium disclosed on a chest roentgenogram led to the clinical recognition of the esophagopericardial fistula . Subsequent emergent pericardiocentesis relieved cardiac tamponade and enabled us to diagnose pyopneumopericardium . A radiographic contrast study with use of meglumine diatrizoate revealed the site of the fistula in the midesophagus . The esophagopericardial fistula was surgically closed, and our patient had a good final result . Formation of an esophagopericardial fistula is a relatively uncommon finding; of the 60 previously reported cases, only 10 patients have survived . As illustrated in the current case, early diagnosis and treatment, including pericardial drainage and intense antibiotic therapy followed by a well-planned operative closure of the fistula, are paramount for the successful management of esophagopericardial fistulas.

J Nucl Med, 1991 Oct, 32(10), 1861 - 5
Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy; Palestro CJ et al.; Seventy-six 111In-labeled leukocyte images performed on 71 patients with possible vertebral osteomyelitis were reviewed . Twenty-eight cases of vertebral osteomyelitis were diagnosed . Vertebral labeled leukocyte activity was normal in 2, increased in 11, and decreased in 15 cases of osteomyelitis . The median duration of symptoms was significantly longer in patients with osteomyelitis and decreased vertebral activity than in patients with osteomyelitis and increased activity (3 mo versus 2 wk; p = 0.019) . No significant relationship between the duration of antibiotic therapy and the appearance of vertebral osteomyelitis on leukocyte images was identified (p = 0.62) . Increased vertebral activity was highly specific (98%) for osteomyelitis but relatively insensitive (39%) . Decreased activity was neither sensitive (54%) nor specific (52%) . Seven patients with clinically resolved infection underwent follow-up imaging . Of four patients who initially presented with increased activity, one had normal and three had decreased vertebral activity on follow up studies . All three patients with decreased activity initially had decreased activity on follow-up . Using increased or decreased activity as criteria for infection, the accuracy of leukocyte imaging for diagnosing vertebral osteomyelitis was 66%, similar to that of 99mTc bone imaging (63%) in our population . Leukocyte imaging did however provide important information about extraosseous infection in 12 of the patients studied.

J Bacteriol, 1991 Oct, 173(19), 6223 - 9
Localization of the lysine epsilon-aminotransferase (lat) and delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (pcbAB) genes from Streptomyces clavuligerus and production of lysine epsilon-aminotransferase activity in Escherichia coli; Tobin MB et al.; Lysine epsilon-aminotransferase (LAT) in the beta-lactam-producing actinomycetes is considered to be the first step in the antibiotic biosynthetic pathway . Cloning of restriction fragments from Streptomyces clavuligerus, a beta-lactam producer, into Streptomyces lividans, a nonproducer that lacks LAT activity, led to the production of LAT in the host . DNA sequencing of restriction fragments containing the putative lat gene revealed a single open reading frame encoding a polypeptide with an approximately Mr 49,000 . Expression of this coding sequence in Escherichia coli led to the production of LAT activity . Hence, LAT activity in S . clavuligerus is derived from a single polypeptide . A second open reading frame began immediately downstream from lat . Comparison of this partial sequence with the sequences of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D valine (ACV) synthetases from Penicillium chrysogenum and Cephalosporium acremonium and with nonribosomal peptide synthetases (gramicidin S and tyrocidine synthetases) found similarities among the open reading frames . Since mapping of the putative N and C termini of S . clavuligerus pcbAB suggests that the coding region occupies approximately 12 kbp and codes for a polypeptide related in size to the fungal ACV synthetases, the molecular characterization of the beta-lactam biosynthetic cluster between pcbC and cefE (approximately 25 kbp) is nearly complete.

J Virol, 1991 Oct, 65(10), 5506 - 12
The stimulatory effect of actinomycin D on avian reovirus replication in L cells suggests that translational competition dictates the fate of the infection; Mallo M et al.; Indirect immunostaining of avian reovirus S1133-infected L-cell monolayers showed that most of the cells can support viral replication . However, the number of cells in which the virus was actually replicating depended on the multiplicity of virus infection . The presence of actinomycin D during infection increased viral protein synthesis, viral growth, and the number of actively infected cells at late infection times . The antibiotic elicited these effects by triggering viral replication in cells that already contained unproductive cytoplasmic virus but that would not get productively infected in the absence of the drug . From these results, we propose a model for the interaction between L cells and avian reovirus S1133 in which viral versus host mRNA competition for the translational machinery determines the fate of the virus infection.

Surg Clin North Am, 1991 Oct, 71(5), 947 - 62
Surgical considerations in the diagnosis and treatment of pelvic inflammatory disease; Soper DE; Pelvic inflammatory disease continues to be a common finding in young women with lower abdominal pain . Typical emergency room pelvic inflammatory disease, with classic symptoms of pain, fever, and a history of high-risk sexual behavior, is easily diagnosed with a high degree of specificity . However, the majority of patients with pelvic inflammatory disease have atypical symptoms, and their condition may be incorrectly diagnosed and treated . Careful attention to the physical signs of pelvic infection and the evaluation of the vaginal secretions for leukocytes improves diagnostic accuracy . Liberal use of diagnostic laparoscopy to confirm the possibility of acute salpingitis is recommended in young women, who have much to lose from a case of untreated salpingitis . Outpatient treatment with a beta-lactam antibiotic followed by a course of doxycycline adequately treats patients with N . gonorrhoeae and C . trachomatis infections . However, patients with suspected anaerobic upper genital tract infection such as those infections associated with tubo-ovarian abscess or IUD use should be admitted for parenteral antibiotic therapy and observation . Laparotomy and extirpative surgery should be reserved for seriously ill patients with generalized peritonitis associated with rupture of a tubo-ovarian abscess and for patients who do not respond to antibiotic therapy . Sound judgment regarding the extent of extirpative surgery, taking into consideration the wishes of the patient with respect to future fertility and hormone production, will lead to an acceptable outcome.

J Pharmacobiodyn, 1991 Oct, 14(10), 583 - 9
Paracellular and transcellular permeabilities of fosfomycin across small intestinal membrane of rat and rabbit by voltage-clamp method; Ishizawa T et al.; The permeability of fosfomycin (FOM), which is a low molecular weight and water-soluble antibiotic, across rat and rabbit jejunal membrane was investigated on a paracellular route and a transcellular route separated by voltage-clamp method . It was determined that FOM permeates through these two routes in both animals . Under a physiologically normal condition, the transmucosal electrical potential difference (about 2 mV), the contribution of the transcellular route to FOM membrane permeability was greater than that of the paracellular route . The transcellular permeability was significantly reduced in the presence of inorganic phosphate . The inhibitory effects of the inorganic phosphate coincided with our reports on FOM uptake by rat jejunal brush-border membrane vesicles in vitro and on FOM absorption by rat jejunal single-pass perfusion in situ.

Minerva Stomatol, 1991 Oct, 40(10), 641 - 9
{Clinico-therapeutic observations on a series of cases of odontogenic abscesses and phlegmons}; Miconi M et al.; The authors review 561 patients suffering from odontogenic abscesses and phlegmons which were large enough to merit hospitalisation in the Division of Maxillo-Facial Surgery of the Odontostomatological Clinic at the University of Turin during the period from 1972 to 1990 . The main features of these septic processes are evaluated: site, size, mode of growth and evolution, tooth responsible . Special attention is paid to the treatment performed: this was essentially based on antibiotic therapy and/or drainage of the abscess via a transcutaneous, transmucous or transdental route . The need to combine medical therapy with surgical drainage of purulent material was noted in the treatment of large infections; in many cases medical therapy alone was unable to guarantee the resolution of the pathology; on the other hand, surgical drainage alone in some cases led to the patient's recovery.

Arch Esp Urol, 1991 Oct, 44(8), 951 - 5
{Controversies over regional lymphadenectomy in carcinoma of the penis}; Cozar Olmo JM et al.; Epidermoid carcinoma of the penis, although rare, is a very aggressive tumor type . The presence or absence of inguinal metastasis is an essential prognostic factor . Treatment of these metastases is one of the current controversies in urological practice; i.e., when and to what extent lymphadenectomy should be performed . Of 24 patients with penile carcinoma, 10 had undergone regional lymphadenectomy over the past 8 years at our institution . Following treatment of the primary penile tumor, 6 patients had palpable inguinal nodes that persisted after treatment with antibiotic and antiinflammatory agents for 6 weeks . Of these, 3 had a positive node biopsy . They were submitted to regional lymphadenectomy which revealed node metastasis in 5 cases (2 pN3, 2 pN2 and 1 pN1) . The patients with no palpable nodes were closely followed and were submitted to lymphadenectomy when these appeared (3 cases) . The fatal outcome of 2 cases (both pN3) prompted us to perform lymphadenectomy prophylactically in the last case, a 40-year-old male with pT2G2 N0 penile cancer . This approach is advocated in patients under 65 with invasive penile carcinoma (pT greater than 1) or a high histological grade of malignancy (G2 and G3).

J Periodontol, 1991 Oct, 62(10), 628 - 33
Resolution of early lesions of juvenile periodontitis with tetracycline therapy alone: long-term observations of 4 cases; Novak MJ et al.; Our previous studies have demonstrated that early-identified lesions of localized juvenile periodontitis (LJP) can be treated by the use of systemically administered tetracycline alone (1 gm/day for 6 weeks) . This therapy results in arrest of disease progression, decreased pocket depths, gains in clinical attachment, and significant repair of alveolar defects . This paper reports on the long-term clinical and radiographic improvement in 4 subjects followed for 1 to 4 years after the completion of tetracycline therapy . Four patients (mean age 14 years) were examined 1 to 4 years following the completion of a single 6 week course of tetracycline . Mean pocket depth was reduced from the initial level of 7.1 mm to 3.6 mm . Mean attachment loss was reduced from 3.8 mm to 0.9 mm and angular bone defects had filled by an average of 72% . Pocket depths and attachment loss continued to decrease during the entire study period, while alveolar bone repair continued to increase . The findings support those of our previous investigation and confirm that: 1) early identified lesions of LJP can be effectively treated with 6 weeks of tetracycline therapy alone; 2) decreases in pocket depth, gains in clinical attachment, and repair of alveolar defects remain stable up to 4 years following antibiotic therapy; 3) clinical and radiographic improvement continues over time and may lead to complete resolution of some lesions; and 4) the reparative/regenerative potential of the periodontium in early onset disease in young individuals may exceed that observed in chronic adult periodontitis.

J Comp Pathol, 1991 Oct, 105(3), 303 - 12
Chronic lesions of thrombo-embolic meningo-encephalomyelitis in calves; Yamasaki H et al.; Six calves showed neurological signs with recumbency for 5 to 30 days . Histologically, they had encephalomyelitis characterized by multiple minute foci of malacia and perivascular microgliosis throughout the central nervous system . Widespread degeneration of the white matter was also detected mainly in the spinal cord . Micro-abscesses and thrombophlebitis, which were occasionally observed in the malacic lesions, suggested that the disease was a feature of infectious thrombo-embolic meningo-encephalomyelitis modified by various factors, including antibiotic therapy.

Am J Anat, 1991 Oct, 192(2), 142 - 68
Short-term morphological response of the rat testis to administration of five chemotherapeutic agents; Russell LD et al.; As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility . Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy . Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident . All except one chemotherapeutic agent (5-FU) caused spermatogonial damage . Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU) . Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX) . The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific.

Spine, 1991 Oct, 16(10), 1146 - 9
Postoperative spinal epidural empyema . Clinical and computed tomography features; Spiegelmann R et al.; Epidural empyema is a rare complication of elective spinal surgery . Four such cases are described . The clinical features of this postoperative complication were surprisingly vague and misleading . Fever was uncommon . Local inflammatory signs or rapid neurologic deterioration were absent . Computerized tomography proved useful in diagnosis and follow-up . Unlike spontaneous spinal epidural abscess, postoperative spinal epidural empyema had a benign course . Causative bacteria were miscellaneous . Surgical evacuation of the purulent collection and appropriate antibiotic therapy resulted in cure in all cases.

Clin Otolaryngol, 1991 Oct, 16(5), 480 - 2
A study of the complications of grommet insertion for secretory otitis media in the presence of nasopharyngeal carcinoma; Skinner DW et al.; Accepted treatment of secretory otitis media, in the presence of nasopharyngeal carcinoma treated with radiotherapy, includes the insertion of a grommet . This study analyses the incidence of otorrhoea following this treatment as compared to a control group . Results show that persistent otorrhoea occurred frequently (68%) in the study group and was refractory to antibiotic therapy . Alternative methods of management of the secretory otitis, such as a hearing aid, should be considered to avoid the complications of grommet insertion in this group of patients.

J Can Dent Assoc, 1991 Oct, 57(10), 799 - 800
Benign mucous membrane pemphigoid: a case report; Miller BA et al.; A relatively rare systemic disease, benign mucous membrane pemphigoid (cicatricial pemphigoid) usually starts in the mouth and is clinically characterized by bullae that rupture and form an ulcer . A distinctive Nikolsky's sign is apparent using gentle air blasts or finger pressure . The pharynx, larynx, nose, esophagus, genitals and eyes can also be affected . Involvement of the conjunctivae can lead to scarring and ensuing blindness . The following case of a healthy 77-year-old man, diagnosed as suffering from mucous membrane pemphigoid, is of particular interest since several confusing clinical observations, including poor oral hygiene, the possibility of a contact dermatitis or an adverse antibiotic reaction, made the diagnosis more difficult . A careful medical history, examination and consultation process is paramount to initiating proper treatment and subsequent relief of symptoms . Benign mucous membrane pemphigoid must always be considered in any patient with desquamative epithelium of the oral mucosa.

J Biomol Struct Dyn, 1991 Oct, 9(2), 251 - 69
Molecular structure of antitumor drug steffimycin and modelling of its binding to DNA; Sriram M et al.; The molecular and crystal structure of steffimycin have been determined by single crystal X-ray diffraction to 0.9 angstrom resolution . The triclinic crystals are in the space group P1, with the unit cell dimensions of a = 8.606(3) angstrom, b = 22.168(7) angstrom, c = 8.448(2) angstrom, alpha = 97.56(3) degrees, beta = 95.97(2) degrees, gamma = 87.94(3) degrees, Z = 2 . The structure was solved by direct methods and refined by the full-matrix least-squares method to a final R value of 0.065 with 3405 (Inet greater than 2.0 sigma (Inet} observed reflections using the NRCVAX software package . The crystal lattice includes 2 independent steffimycin, 3 water and one 2-methyl-2,4-pentanediol molecules . The conformation of steffimycin is grossly similar to other anthracycline antibiotics including daunorubicin . The crystal packing interactions of steffimycin suggest a preferred stacking of the aglycone chromophore of the antibiotic which resembles the intercalative interactions seen in the daunorubicin-d(CGTACG) (Wang et al., Biochemistry 26, 1152 (1987} and nogalamycin-d(CGT(pS)ACG) (Liaw et al., Biochemistry 28, 9913 (1989} complexes . The atomic coordinates data from these complexes were used to model the intercalative binding of steffimycin to DNA . The models were then stereochemically idealized by the constraint refinement program NUCLSQ . Subsequently XPLOR software package was used for energy minimization of these models in vacuo . The model building studies suggest that steffimycin has a higher CpG base sequence specificity over the TpA step, similar to that of daunorubicin and nogalamycin.

Drugs, 1991 Oct, 42(4), 606 - 15
Therapeutic dilemmas in external ocular diseases; Asbell PA et al.; Three ocular conditions continue to pose therapeutic dilemmas for the practising clinician . Acanthamoeba keratitis, which presents with ocular pain, redness, tearing, photophobia and lid oedema, should be considered in any chronic, progressive corneal ulceration that is unresponsive to conventional treatment . Although the best treatment for this infection has yet to be defined, surgery should be reserved for those patients with progressive destructive disease or corneal penetration . Topical antibiotics and oral ketoconazole may be beneficial, as may surgical debridement in conjunction with topical antibiotic-antifungal combinations . However, since more than two-thirds of reported cases involve contact lens wearers, patients should be instructed as to the importance of regular lens care regimens . Giant papillary conjunctivitis occurs more frequently in soft contact lens wearers than in those wearing hard lenses, but may also occur in association with ocular prostheses, cataract surgery and corneal transplants . Symptoms of increased lens awareness, mucus accumulation, itching and blurred vision occur . Stopping use of contact lenses usually improves or eliminates these irritating effects, but is not always practical . Thus, resolution or improvement of symptoms while the patient continues to wear contact lenses is desirable, making lens hygiene essential in treatment . Pharmacological treatment includes the use of topical corticosteroids and agents that stabilise mast cells, such as cromolyn sodium . The dry eye syndrome can occur alone or as a part of Sjogren's syndrome . The irritation, redness, and other symptoms associated with ocular dryness are usually treated by preparations of either mucomimetics, polyvinyl alcohol or cellulose derivatives, which provide moisture and prevent evaporation from the surface of the eye.

J Antibiot (Tokyo), 1991 Oct, 44(10), 1141 - 7
The effect of sinefungin and synthetic analogues on RNA and DNA methyltransferases from Streptomyces; Yebra MJ et al.; Sinefungin is an antibiotic structurally related to S-adenosylmethionine . It has been described as an inhibitor of RNA transmethylation reactions in viruses and eukaryotic organisms, but not in bacteria . We show here that sinefungin strongly inhibits RNA methyltransferase activity, but not the biosynthesis of these enzymes in Streptomyces . All the methylated bases found in Streptomyces RNA (1-methyladenine, N6-methyladenine, N6,N6-dimethyladenine and 7-methylguanine) are inhibited by this antibiotic . Experiments with sinefungin analogues show that specific changes in the ornithine radical of the molecule still preserve its inhibitory capability . The substitution of the adenine radical by uridine causes the loss of the inhibitory effect . These results and our former studies on Streptomyces DNA methylation, suggest that nucleic acid modification is the main target of sinefungin in Streptomyces.

Hepatogastroenterology, 1991 Oct, 38(5), 377 - 87
The treatment of chronic hepatic encephalopathy; Morgan MY; The neuropsychiatric abnormalities which accompany cirrhosis of the liver vary widely from subclinical impairment of psychometric performance to overt episodic or persistent changes in cerebral function . The pathogenesis of the syndrome is unknown although important roles are ascribed to circulating gut-derived toxins of nitrogenous origin and to changes in central neurotransmission, particularly of the dopaminergic and GABA-ergic systems . Treatment is, therefore, based on mechanisms to reduce the production and absorption of gut-derived toxins such as decreasing and modifying dietary protein intake, altering the intestinal bacterial flora and bowel cleansing, and on mechanisms designed to modify central neurotransmitter balance either directly by use of dopaminergic agents or benzodiazepine antagonists or indirectly by use of amino-acid mixtures . Some treatment measures, such as use of non-absorbable disaccharides and vegetable protein diets, are known to be efficacious, and are the mainstays of management for all forms of the syndrome . Others are used in more specific circumstances, for example the antibiotic neomycin is effective during acute exacerbations of the syndrome, and the dopamine agonist bromocriptine provides benefit when symptoms are persistent and intractable . Certain treatments such as branched-chain amino acids and the benzodiazepine antagonist, flumazenil, are at present, of unproven value.

Biochemistry, 1991 Sep 17, 30(37), 8936 - 44
Opposite facial specificity for two hydroquinone epoxidases: (3-si,4-re)-2,5-dihydroxyacetanilide epoxidase from Streptomyces LL-C10037 and (3-re,4-si)-2,5-dihydroxyacetanilide epoxidase from Streptomyces MPP 3051; Shen B et al.; (3-si,4-re)-2,5-Dihydroxyacetanilide epoxidase (DHAE I), a key enzyme in the biosynthesis of the epoxysemiquinone antibiotic LL-C10037 alpha by Streptomyces LL-C10037 {Gould, S.J., & Shen, B . (1991) J . Am . Chem . Soc . 113, 684-686}, and (3-re,4-si)-2,5-dihydroxyacetanilide epoxidase (DHAE II) isolated from Streptomyces MPP 3051--which yields the (3R,4S)-epoxyquinone mirror image product of DHAE I--are described . DHAE I was purified 640-fold . Gel permeation chromatography indicated an Mr of 117,000 +/- 10,000; SDS-PAGE gave a major band of 22,300 daltons, indicating that DHAE I is either a pentamer or hexamer in solution . The enzyme had a pH optimum of 6.5, a Km of 8.4 +/- 0.5 microM, and a Vmax of 3.7 +/- 0.2 mumol min-1 mg-1 . DHAE II was purified 1489-fold . The enzyme was shown to be a dimer of Mr 33,000 +/- 2000, with 16,000-dalton subunits, with a pH optimum of 5.5 and a Km of 7.2 +/- 0.4 microM . Both enzymes required only O2 and substrate; flavin and nicotinamide coenzymes had little or no effect . Neither catalase nor EDTA affected the activity of either enzyme, but complete inhibition of both was obtained with 1,10-phenanthroline . The activity of the purified DHAE I could be enhanced, but only by Mn2+ (relative V = 246 at 0.04 mM), Ni2+ (relative V = 266 at 0.2 mM), or Co2+ (relative = 498 at 0.2 mM) . Reconstitution from a DHAE I apoenzyme, generated by treatment with 1,10-phenanthroline followed by Sephadex G-25 chromatography, occurred only by addition of one of these three metals.(ABSTRACT TRUNCATED AT 250 WORDS)

J Biol Chem, 1991 Sep 15, 266(26), 17707 - 12
Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells; Yoshimori T et al.; Bafilomycin A1 is known as a strong inhibitor of the vacuolar type H(+)-ATPase in vitro, whereas other type ATPases, e.g . F1,F0-ATPase, are not affected by this antibiotic (Bowman, E.M., Siebers, A., and Altendorf, K . (1988) Proc . Natl . Acad . Sci . U.S.A . 85, 7972-7976) . Effects of this inhibitor on lysosomes of living cultured cells were tested . The acidification of lysosomes revealed by the incubation with acridine orange was completely inhibited when BNL CL.2 and A431 cells were treated with 0.1-1 microM bafilomycin A1 . The effect was revealed by washing the cells . Both studies using 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine and fluorescein isothiocyanate-dextran showed that the intralysomal pH of A431 cells increased from about 5.1-5.5 to about 6.3 in the presence of 1 microM bafilomycin A1 . The pH increased gradually in about 50 min . In the presence of 1 microM bafilomycin A1, 125I-labeled epidermal growth factor (EGF) bound to the cell surface at 4 degrees C was internalized normally into the cells at 37 degrees C but was not degraded at all, in marked contrast to the rapid degradation of 125I-EGF in the control cells without the drug . Immunogold electron microscopy showed that EGF was transported into lysosomes irrespective of the addition of bafilomycin A1 . These results suggest that the vacuolar type H(+)-ATPase plays a pivotal role in acidification and protein degradation in the lysosomes in vivo.

Infect Dis Clin North Am, 1991 Sep, 5(3), 437 - 52
Bronchoscopic protected specimen brush and bronchoalveolar lavage in the diagnosis of bacterial pneumonia; Broughton WA et al.; Despite marked improvements in antibiotic therapy, the accurate diagnosis and treatment of bacterial lower respiratory tract infection remain a challenge . The bronchoscopic protected specimen brush and bronchoscopic bronchoalveolar lavage combined with quantitative bacterial cultures can provide sensitive and relatively specific information about lower airway flora . Both of these methods require strict observance of the required protocol, careful processing of the obtained specimens, and the absence of prior antibiotic therapy to obtain best results . These procedures are also of some utility in sickle cell acute chest syndrome, bronchiectasis, and in the immunocompromised host.

Clin Exp Rheumatol, 1991 Sep-Oct, 9(5), 519 - 23
Osteomyelitis in a patient with a chronically infected arterial graft and longstanding hypertrophic osteoarthropathy of the leg; Maertens M et al.; A patient is reported with hypertrophic osteoarthropathy of the right leg who developed an osteomyelitis; this appeared to be related to an infected aortic bifurcation prosthesis with increased uptake on leukocyte scan and chronic gas formation at the proximal aortic anastomosis on computed tomography . There have been previous reports of hypertrophic osteoarthropathy as a sign of arterial prosthesis infection . In this patient antibiotic therapy was successful in controlling the osteomyelitis but eradication of the arterial prosthesis infection could not be confirmed and an elective arterial operation involved too great a risk.

Ann Pediatr (Paris), 1991 Sep, 38(7), 503 - 8
{Evaluation of tixocortol pivalate-neomycin combination versus ++a placebo excipient in acute rhinopharyngitis in children}; Reinert P et al.; Effectiveness and clinical tolerance of the tixocortol-neomycin combination (Pivalone-Neomycin nasal suspension) used as monotherapy were evaluated in a double-blind placebo-controlled study (placebo: vehicle i.e., N-cetylpyridinium chloride, sodium chloride, sodium hydroxide solution, benzyl alcohol, purified water, monosodium phosphate) in 211 pediatric patients (aged 6 months to 8 years) with uncomplicated acute rhinopharyngitis . After seven days therapy, improvement in symptoms of acute rhinopharyngitis, especially rhinorrhea and nocturnal cough, was greater in the tixocortol-neomycin group . Physical evaluation documented significant improvements in local superinfection with disappearance of mucopurulent nasal secretions and posterior drip . Locoregional outcome, evaluated on severity of infectious complications and antibiotic use, was also more favorable in the tixocortol-neomycin group . These results, together with the good clinical tolerance of the study drug, demonstrate the value of single-drug therapy with this local corticosteroid-neomycin combination in children with uncomplicated acute rhinopharyngitis . They confirm that local administration of corticosteroids to combat inflammatory phenomena is useful not only in the well-recognized lower respiratory tract indications (asthma, respiratory syncitial virus infections) but also in nasal diseases (rhinitis).

Ann Otol Rhinol Laryngol, 1991 Sep, 100(9 Pt 1), 768 - 73
Massive orofacial abscesses of dental origin; Welsh LW et al.; Massive cervicofacial abscesses of dental origin are relatively rare, and may be associated with serious and grave morbidity . In extreme cases, an occasional fatality may result from regional complications . Three cases are presented that describe the clinical and radiographic evaluation and the surgical approaches for abscess drainage . Specific attention is directed toward 1) the management of imminent airway obstruction, 2) the application of computed tomographic technology for localization and surgical planning, and 3) current antibiotic therapy.

Scand J Gastroenterol, 1991 Sep, 26(9), 927 - 32
Transmission of Helicobacter pylori infection . Studies in families of healthy individuals; Malaty HM et al.; Helicobacter pylori is accepted as the commonest cause of type-B gastritis . Detailed information about the mode of transmission remains scanty . We investigated the frequency of H . pylori infection within families, defined as consisting of a husband and wife with at least one biologic child, all living in the same household . Inclusion criteria required that both the parents and the children had been born in the United States, had used no antibiotic or bismuth for the previous 2 months, had no recent major illness or surgical operation, and had no symptoms referable to the upper gastrointestinal tract . H . pylori infection was identified with a 13C-urea breath test and an enzyme-linked immunosorbent assay for anti-H . pylori IgG . Forty-one families (151 healthy individuals) were enrolled . Before the results of the H . pylori tests were known, one parent was selected as the index subject . H . pylori infection clustered; that is, 68% of spouses of H . pylori-infected index subjects were also H . pylori-infected, compared with 9% of spouses of H . pylori-negative index subjects (p less than 0.0001) . The children of infected index parents were also more likely to be infected than children of uninfected index parents--40% versus 3%, respectively (p less than 0.0001)--and the results in the children were independent of whether the father or the mother was the index subject . Clustering of H . pylori infection within families suggests person-to-person transmission or common source exposure . The high frequency of H . pylori infection in spouses suggests that genetic factors are less important than living conditions for transmission of H . pylori infection.

J Antibiot (Tokyo), 1991 Sep, 44(9), 925 - 33
Structure of aureobasidin A; Ikai K et al.; Aureobasidin A, a new antifungal antibiotic, was isolated from the culture medium of Aureobasidium pullulans R106 . Aureobasidin A was a cyclic depsipeptide consisting of eight alpha-amino acid units and one hydroxy acid unit . The structures of the units were found by acid hydrolysis of the antibiotic to be 2(R)-hydroxy-3(R)-methylpentanoic acid, beta-hydroxy-N-methyl-L-valine, N-methyl-L-valine, L-proline, allo-L-isoleucine, N-methyl-L-phenylalanine, L-leucine, and L-phenyl-alanine . The sequence of the units was identified by NMR and FAB-MS of the products from the alkaline hydrolysis of aureobasidin A.

J Antibiot (Tokyo), 1991 Sep, 44(9), 1006 - 12
Conversion of bialaphos to other oligopeptides containing phosphinothricin by Streptomyces hygroscopicus; Kumada Y et al.; Two oligopeptides containing phosphinothricin were accumulated in the culture of bialaphos (BA) producer Streptomyces hygroscopicus SF1293 when large amount of BA was added to the culture at idio phase . One of the oligopeptides was a new substance, BA dimer (phosphinothricyl-alanyl-alanyl-phosphinothricyl-alanyl-alan ine), and the other was a known substance called If (phosphinothricyl-alanyl-alanyl-phosphinothricin) . Though BA none producing mutants which were blocked at the steps 1, 10 and 13, respectively in BA biosynthesis also converted BA to BA dimer and If, the mutants blocked at the step 11 (alanylation) could not curry out the conversion . Antibiotic activities of BA dimer and If were lower than 1/100 of BA.

J Med Chem, 1991 Sep, 34(9), 2821 - 3
Monoterpenic fragment analogues of aplasmomycin as potential antimalarial; Balu N et al.; Seven analogues of monoterpenic fragment of aplasmomycin were synthesized as targeted antimalarial agents . The potency of the compound 6 was comparable with the sesquiterpene lactone artemisinin and the antibiotic aplasmomycin in vivo against Plasmodium berghei yoelli.

Invest Ophthalmol Vis Sci, 1991 Sep, 32(10), 2696 - 9
Coryneform group A-4 endophthalmitis . An experimental animal model; McManaway JW 3rd et al.; Diphtheroids, members of the coryneform family of bacteria, increasingly have been recognized as the cause of serious ocular diseases . After isolation of coryneform group A-4 from two patients with delayed endophthalmitis after cataract extraction and intraocular lens implantation, 10(7) organisms were injected into the vitreous of seven New Zealand white rabbits, producing endophthalmitis in all eyes inoculated . Coryneform group A-4 subsequently was isolated in six of seven eyes receiving 10(7) organisms, proving Koch's postulates . Five of these seven eyes were treated with a single dose of intravitreal gentamicin, and three eyes remained culture positive . Eyes inoculated with 10(5) or 10(2) coryneform group A-4 organisms had transient anterior chamber and vitreal inflammation; all vitreous cultures were negative . These studies demonstrate that coryneform group A-4 endophthalmitis can be reproduced in an animal model and that gentamicin may not sterilize an eye infected with this organism . Future studies are needed to determine the optimum antibiotic regimen for treatment of this type of endophthalmitis.

Arch Intern Med, 1991 Sep, 151(9), 1809 - 12
Iatrogenic renal disease; Davidman M et al.; We studied iatrogenic problems in nephrology by classifying all patients for nephrology consultation into nine presenting syndromes and seven etiologic groups . One hundred (2.2%) of all admissions were seen in nephrology consultation . Acute renal failure was the most common presenting syndrome, accounting for 59% of the consultations . Forty-one of the 100 consultations (1% of all admissions) had a renewal syndrome of iatrogenic origin . Of these 41 patients, 38 had acute renal failure and three had fluid and electrolyte problems . Twenty of the 41 patients had drug-induced problems . Eighteen of these patients were dehydrated, and in three patients, acute renal failure occurred after surgery . Of the 20 patients with iatrogenic renal problems caused by drugs, seven problems were antibiotic related, five were due to diuretics, four were due to nonsteroidal anti-inflammatory drugs, three were due to angiotensin-converting enzyme inhibitors, and one was from the use of contrast medium . The 41 patients with iatrogenic-related renal disease were older than the other 59 patients (61.8 vs 49.3 years) . Iatrogenic renal disease developed in 1% of all patients admitted to a tertiary care hospital, and 12% of these patients died . The most common renal syndrome is acute renal failure, most often caused by nephrotoxic drugs . The incidence can probably be decreased by better monitoring of body weight and fluid balance to prevent dehydration and by the avoidance of nephrotoxic drugs.

J Surg Res, 1991 Sep, 51(3), 223 - 8
Effect of controlled hemorrhage on tissue and serum cefazolin clearance; Brothers TE et al.; Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits . Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels . Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion . Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min . Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01) . The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals . More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.

J Gerontol Nurs, 1991 Sep, 17(9), 30 - 4
Iatrogenesis in the elderly . Nosocomial infections; Stolley JM et al.; The elderly are increasingly susceptible to nosocomial infection because of age-related changes and the presence of multiple chronic illness . Epidemics frequently occur in long-term care facilities with upper respiratory infections, diarrhea, conjunctivitis, and antibiotic-resistant bacteria the most common . Other common nosocomial infections are those of the respiratory tract, gastrointestinal tract, genitourinary system, and integumentary system . Infection control programs, systematic surveillance, regular inservice programs on infection control (especially handwashing), and employee and resident health programs can be instituted to decrease the incidence of nosocomial infections.

Arch Otolaryngol Head Neck Surg, 1991 Sep, 117(9), 984 - 9
Systemic steroids for otitis media with effusion in children; Rosenfeld RM et al.; The role of oral steroids in the treatment of otitis media with effusion in children is the subject of ongoing debate . To critically evaluate the existing evidence, we performed a formal meta-analysis of six randomized clinical trials (n = 264 children) selected from 14 articles and abstracts . Children receiving steroids for 7 to 14 days were 3.6 times more likely than placebo-treated control subjects to have both ears free of effusion at the end of therapy (95% confidence interval, 2.2 to 4.1) . This finding was essentially unchanged when the studies were weighted by a quality score, or stratified by use of concurrent antibiotic . The presence of significant heterogeneity among these studies suggests that additional trials will be needed to identify the specific subset(s) of children most likely to benefit from steroid therapy.

Obstet Gynecol, 1991 Sep, 78(3 Pt 2), 542 - 3
Laparoscopic treatment of painful perihepatic adhesions in Fitz-Hugh-Curtis syndrome; Owens S et al.; This report illustrates a case of Fitz-Hugh-Curtis syndrome associated with pelvic inflammatory disease in which the clinical symptom of right upper quadrant pain was severe and persistent despite appropriate antibiotic therapy . Because of the atypical course, an extensive work-up was performed to rule out other possible etiologies for the pain . In this context, a laparoscopy was performed and identified dense adhesions between the liver and the anterior abdominal wall . These adhesions were safely and successfully lysed using a KTP/532 laser through a second puncture site . After surgery the pain was completely resolved, with no further recurrence after 6 months of follow-up.

Klin Oczna, 1991 Sep, 93(9), 262 - 3
{Late results of the treatment of suppurative endophthalmitis by vitrectomy}; Nawrocka Z; The authoress discusses the late results of treatment in 14 patients with infective endophthalmitis by vitrectomy . She compared the results of treatment of 13 patients with the same condition treated by conventional methods . The received data enabled to confirm the thesis that vitrectomy combined with an intraocular antibiotic therapy is a method of choice in the treatment of purulent endophthalmitis . The late observations demonstrated that favourable results have a lasting character.

Kitasato Arch Exp Med, 1991 Sep, 64(2-3), 123 - 32
Taxonomic properties of five Kitasatosporia strains isolated by a new method; Takahashi Y et al.; Kitasatosporia strains were found to be resistant to an antibiotic, novobiocin . By a new method using novobiocin-containing agar medium, five Kitasatosporia strains, SK-3255, OM-5023, SK-3406, SK-3412 and SK-3421 were efficiently isolated from soils . These five strains were characterized in common by Rectiflexibiles, spores cylindrical with smooth surfaces, and no melanin formation . Two strains, SK-3255 and OM-5023 were taxonomically different from known species of the genus Kitasatosporia, while the two strains, SK-3406 and SK-3412 and the remaining strains SK-3421 were identified with K . phosalacinea and K . papulosa, respectively.

Neurol Neurochir Pol, 1991 Sep-Oct, 25(5), 683 - 8
{A case of primary abscess of the pituitary gland}; Podgorski JK et al.; This report details the management of a patient with a primary pituitary abscess with secondary amenorrhea, mimicking pituitary adenoma . The preoperative diagnosis of intra- and suprasellar pituitary abscess was established by X-ray examination of the skull, CT-scans and anamnesis . After transsphenoidal removal of the abscess with accompanying antibiotic therapy the patient had a progressive and nearly complete recovery with normalization of menstruation.

Infection, 1991 Sep-Oct, 19(5), 331 - 5
Infections and other illnesses of children in day-care centers in Helsinki . II: The economic losses; Nurmi T et al.; The economic consequences of illnesses among children in day-care centers (DCCs) were estimated in Helsinki during a one-year period, 1985-1986 . The municipal DCCs took care of altogether 14,882 children at the end of 1985 . In terms of money value in 1990, the total loss due to illnesses among all DCC children was $22,485,000 (1 US dollar = 3.80 FIM) . Nearly half (46%) of this loss was caused by illnesses among children under three years of age, although these represent only 20% of the children in day care . The losses were $3,535 per child place in use among children under three years of age and $1,012 among older children . Economic losses due to the guardian's absence from work totalled $1,623, deficient utilization of DCCs $1,254, visits to a physician $169, hospitalization $221, paid care of children at home $219 and antibiotic courses $12 per child place in use for those under the age of three years . The corresponding figures for older children were 541, 248, 95, 51, 73 and 4 dollars per child . More than 90% of illnesses and costs were caused by infectious diseases . Because the costs due to illnesses among children under three years of age were more than three times as high as those for older children, preference should be given to home care and family day care for younger children and efforts should be made to find out how to build healthy DCCs for them.

Biochem Cell Biol, 1991 Sep, 69(9), 618 - 23
Kinetics of a rapid, luminol dependent chemiluminescence signal induced in HL-60 cells by amphotericin B and other stimulants; O'Keefe DA et al.; Addition of the polyene antibiotic amphotericin B or tissue culture medium to nondifferentiated HL-60 cells in the presence of luminol induces a chemiluminescence signal that reaches a peak value within a few seconds and decays exponentially in less than a minute . The kinetics of the signal and its modulation by superoxide dismutase, catalase, and horseradish peroxidase are consistent with a series of solution biochemical processes with a rate-determining step corresponding to the disproportionation of a luminol-superoxide complex . The effects of the enzymes demonstrate that superoxide is a precursor to the rate-determining intermediate and that both catalase and peroxide enhance a reaction that competes with the rate-limiting process.

J Diarrhoeal Dis Res, 1991 Sep, 9(3), 250 - 7
Diarrhoeal disease morbidity, risk factors and treatments in a low socioeconomic area of Ilorin, Kwara State, Nigeria; Oni GA et al.; A 12-month diarrhoeal disease surveillance was carried out in a sample of 351 children under 3 years of age in a low-income traditional area of Ilorin, Nigeria to determine whether sociodemographic characteristics, including age of the child, sex, parity, mother's education, occupation, mother's age and household kitchen, were associated with the incidence of acute diarrhoea . Bivariate and multivariate analyses were used to determine association . Results indicated that only the age of the child and the type of kitchen used by the household had a significant association with diarrhoea . Diarrhoeal incidence decreases with the child's age while households with a private kitchen had a significantly lower incidence rate than those without a kitchen . This finding emphasises the importance of good hygiene in reducing the risk of having diarrhoea . Three common treatments applied by mothers are ORS (used in 14.8% of diarrhoea days), antibiotics (54.5%) and local herbs (27.7%) . The younger a child is the more likely that ORS and antibiotics will be administered during diarrhoea . About 53% of the antibiotic use was by self medication while 40% were prescribed by the clinics . The need for educational campaigns to discourage the inappropriate use of antibiotics was emphasised.

J Diarrhoeal Dis Res, 1991 Sep, 9(3), 227 - 34
Evaluation of clinical management training programme for diarrhoea; Salazar-Lindo E et al.; We report the evaluation of a training programme on clinical management of infantile diarrhoea . The training programme was delivered through a series of on-site clinical courses offered to a selected group of physicians and nurses from 16 health units in Peru and a series of local workshops conducted in their own health units . The outcome of this training programme was assessed by pre- and post-tests, knowledge, attitude, and practice (KAP) questionnaires, and observational surveys . A significant improvement in medical knowledge about diarrhoea, in particular about the use of ORT and drug therapy, was observed . Although the observational surveys showed significant improvement in the use of ORT at health facilities (2.9% to 23.6%, p = 0.007) the rate observed was still low compared to the high level of knowledge on ORT that was demonstrated by the KAP questionnaires . A reduction of antibiotic prescription for inpatients with diarrhoea (85.7% to 64.8%, p = 0.025) was observed . The training programme was also effective in promoting the establishment of Oral Rehydration Units in the participants' health facilitiesPIP: Physicians designed a training program on clinical management of diarrhea which consisted of 11 clinical training courses at the Cayetano Heredia University Hospital in Lima, Peru for 37 physicians and 37 nurses from 16 hospitals in 20 various cities in Peru; a number of local workshops on overall features of clinical management of diarrhea cases; and supervisory pre- and posttraining visits to the hospitals . Health workers treated only 2.9% of dehydration cases and 25.7% of inpatient diarrhea cases before dehydration set in and 7.7% of similar outpatients with oral rehydration therapy (ORT) during the pretraining observational survey . After the training, these corresponding figures increased to 23.6% (p=.007), 57.6% (p=.002), and 88.9% (p.0001) . The 23.6% rate was still low compared with the high level of knowledge about diarrhea treatment, however . Before training, they prescribed antibiotics to 85.7% of inpatients and 50% of outpatients . After the training, health workers still prescribed antibiotics to 50% of outpatients even though 95% knew correct drug prescription practices . On the other hand, they prescribed antibiotics to a lower percentage of inpatients (64.8%; p=.025) . Before the course, they recommended breast feeding and weaning foods in 25.7% and 28.6% of inpatients, respectively, and in 47.1% and 41.2% of outpatients, respectively . Following the course, health workers were more likely to advise breast feeding and weaning foods for outpatients (p=.015 and p=.001, respectively), but tended not do so for inpatients . They were less likely to recommend breast feeding (25.7% vs . 19.4%) . This evaluation helped promote creation of rehydration units in 12 of the participating hospitals . The results showed a need for continuous medical education for the health workers in the new units .

Antibiot Khimioter, 1991 Sep, 36(9), 29 - 31
{Comparative levels of amphotericin B in the skin and subcutaneous fatty tissue after cutaneous application of amphotericin ointment by phonophoresis and with preliminary treatment by dimethyl sulfoxide}; Romanenko IM et al.; A comparative study of the amphotericin B contents in the skin and subcutaneous fatty tissue was performed on guinea pigs after local application of amphotericin ointment by phonophoresis and with preliminary treatment of the skin by dimethyl sulfoxide (DMSO) . When the amphotericin ointment was used in combination with ultrasound the content of amphotericin B in the skin and subcutaneous fatty tissue 1, 3, 24, 48 and 72 hours after the application was much higher than that after the ointment local application without the ultrasonic treatment . When the amphotericin ointment was applied locally after the preliminary treatment with DMSO the maximum content of the antibiotic in the skin and subcutaneous fatty tissue was observed 3 hours after the application which was significantly higher than the content observed after the ointment application by phonophoresis and especially locally without the ultrasonic treatment . In 24, 48 and 72 hours the amphotericin B concentration in the skin and subcutaneous fatty tissue under any conditions lowered and in 24 hours had a tendency to level in the areas treated with ultrasound and DMSO . In 48 and 72 hours the highest concentrations of the antibiotic were in the skin and subcutaneous fatty tissue after the ointment application by phonophoresis.

Antibiot Khimioter, 1991 Sep, 36(9), 27 - 9
{Immunogenic properties of neomycin conjugates with macromolecular carriers}; Nemtsova NN et al.; To obtain diagnostic antibodies to neomycin, immunogenic properties of the neomycin conjugates with macromolecular carriers were studied . Bovine serum albumin and copolymers of N-vinylpyrrolidone with crotonic acid and N-hydroxyphthalimide ether of crotonic acid were used as carriers . It was shown that immunization of mice by the conjugates in combination with Freund's adjuvant resulted in production of neomycin antibodies, the titer being 1/80 to 1/130 . When the antibiotic conjugates with the copolymers of N-vinylpyrrolidone were used and not the neomycin conjugates with the carrier of the protein nature, the neomycin antibodies were produced in the absence of Freund's full adjuvant . With the use of the isolated antibodies to neomycin a method for indirect solid phase enzyme immunoassay of neomycin was developed at the minimum detectable level of 25 ng/ml.

J Inorg Biochem, 1991 Sep, 43(4), 717 - 22
The effect of some platinum compounds on the activity of the CTP synthetase of Ehrlich ascites tumor cells: in vitro and in vivo studies; Ganeva RL et al.; The present work investigates the effect of cis-DDP (DDP, diamminedichloroplatinum(II)), trans-DDP, SPC (spermine platinum(II) complex), and K2PtCl4 on the activity of the CTP synthetase in the cytosol of Ehrlich ascites tumor cells . To study their in vitro effect, the platinum compounds were supplemented to the incubation mixture for the enzyme assay . A concentration dependent inhibition of the CTP synthetase was found which was strongest in the case of trans-DDP . When ascites cells collected from mice, pretreated in vivo with platinum compounds, were used, the enzyme assay showed that the inhibition is strongest in the case of cis-DDP and K2PtCl4 (about 90% inhibition) . This distinct inhibitory effect of the platinum compounds in the present experiments may be explained with the metabolic conversions of the compounds in the organism to their more active forms and/or with the inhibition of the protein biosynthesis under their influence because the lifetime of the CTP synthetase is short . This last assertion is proved in this work by control experiments with the antibiotic cycloheximide, which is an inhibitor of the protein biosynthesis.

Compr Ther, 1991 Sep, 17(9), 35 - 8
The role of Helicobacter pylori in gastroduodenal disease; Wang KK; Peptic ulcers are the result of a wide variety of factors, with H . pylori probably being one of the more significant . H . pylori has been most strongly associated with gastritis and duodenal ulcer disease . The relationship of H . pylori to gastric ulcers is less substantial . The eradication of H . pylori can be achieved in the majority of patients with triple antibiotic therapy . However, resistance to metronidazole occurs readily . Eradication of H . pylori can change the course of duodenal ulcer disease by decreasing recurrence rate from 80% to zero . Nonetheless, treatment for H . pylori should only be done in randomized trials at the current time because of the lack of completely effective therapy and the high risks of side effects . The mechanism by which H . pylori influences duodenal ulcer recurrence is unclear . Pathogenic mechanisms of the organism also need to be further elucidated.

Am J Perinatol, 1991 Sep, 8(5), 338 - 41
Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact; Maberry MC et al.; Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage . We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin) . The frequency of vaginal and cesarean delivery was similar in both groups . There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS) . There were no significant differences in either neonatal morbidity or mortality . The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally.

Vopr Med Khim, 1991 Sep-Oct, 37(5), 33 - 5
{The effect of actinomycin D on lysosomal proteinase activity in murine macrophages and spleen during immune response}; Vasil'ev AV et al.; Actinomycin D inhibited activation of lysosomal cathepsins A, B, C, D, H and L in peritoneal macrophages, caused by T-dependent antigen (sheep erythrocytes), of mice CBA X C57BL/6 strain . At the same time, the antibiotic stimulated activity of cathepsins A, C, D and H but decreased content of antibody-producing cells in spleen tissue . Inhibition of lysosomal proteinases in macrophages may be responsible for immunodepressive effect of actinomycin D.

Tex Med, 1991 Sep, 87(9), 62 - 6
Lyme borreliosis in Texas; Goldings AS et al.; Lyme borreliosis is a protean infection caused by B burgdorferi, a recently recognized arthropod-borne spirochete . The disease is generally acquired during warm weather, and its onset is characterized by a skin lesion, EM, and flulike symptoms . Neurologic, cardiac, and/or rheumatologic abnormalities may emerge weeks, months, or years later . In the absence of the pathognomonic skin lesion, determination of antibody response is currently the most practical laboratory aid in diagnosis . However, clinical judgement is necessary for the correct interpretation of laboratory results because false-positive and false-negative results are common . Antibiotics remain the mainstay of therapy . Longer courses of antibiotic therapy than those previously recommended may be needed to obtain a cure, particularly in later stages of the illness.

Neuroreport, 1991 Sep, 2(9), 505 - 8
Embryonic mouse spinal cord motor neuron hybrid cells; Salazar-Grueso EF et al.; Studies of motor neurons are difficult because of limitations in their isolation and culture . One solution is to produce clonal neural hybrid cells that can express motor neuron characteristics; we fused an aminopterin-sensitive and neomycin-resistant mouse neuroblastoma cell line to isolated embryonic mouse spinal cord motor neurons . Several hybrid neuron cell lines expressing high levels of choline acetyltransferase (CHAT) enzyme activity were found . These were cloned and clones with high CHAT activity isolated . The hybrid nature of cloned cells was confirmed by karyotyping and determining glucose phosphate isomerase allozymes . The availability of these embryonic clonal hybrid cells will enable molecular, physiological, and biochemical studies to define motor neuron-specific properties.

Int Ophthalmol, 1991 Sep, 15(5), 343 - 5
Congenital ichthyosis in a Libyan child with ophthalmic manifestations; Elshtewi M et al.; This report presents a Libyan child with congenital ichthyosis of the recessive lamellar variety complicated by severe ectropion of both upper and lower eyelids . Over a period of 12 months the degree of ectropion diminished and the anterior segments of the eyes were preserved using regular lubricating drops, vitamin A ointment and intermittent topical antibiotic therapy . Despite the pronounced initial upper eyelid ectropion no surgery was required to relieve the ectropion or prevent corneal exposure.

Ital J Gastroenterol, 1991 Sep-Oct, 23(7), 403 - 7
Rifaximine versus neomycin in the treatment of portosystemic encephalopathy; Di Piazza S et al.; In 14 patients with cirrhosis and chronic portosystemic encephalopathy, the effectiveness of treatment with a new non-assorbable antibiotic (rifaximine) was compared to neomycin . The parameters evaluated were: bradylalia, flapping tremor, performance, visual evoked potentials and the trial making test . Both treatments were combined with lactulose . The analysis of results showed a rate of positive results in the patients treated with rifaximine greater than that with neomycin . Differences, however, were not significant.

Ukr Biokhim Zh, 1991 Sep-Oct, 63(5), 33 - 8
{Dynamics of RNA synthesis and transport into the intact and regenerating rat liver in the presence of sublethal doses of actinomycin D}; Bozhkov AI et al.; The time-dependent characteristic of RNA synthesis has been studied against the effect of sublethal doses of actinomycine D in cells with different proliferative activity, connection of synthesized RNA with RNP-particles of nuclei and its transport into the ribosomes and cytoplasmic postribosomal fraction . Against a background of actinomycine D sublethal doses (150 and 300 micrograms per 100 g body weight) from 0.5 to 4% of RNA is synthesized in comparison with the original level . The level of specific radioactivity of RNA depends on the original functional state of the liver . The newly synthesized RNA is found in the nuclei RNP-particles and transported into the cytoplasm . It is localized in ribosomes (2-3% in intact and about 6% in regenerating liver from the original level) and in the postribosomal fraction (8-10% and 16-18% in intact and regenerating liver, respectively . It is supposed that RNA synthesized against the effect of sublethal doses of actinomycine D takes part in conservation and restoration of realization of genetic information system activity, that is observed 12 hours after the antibiotic injection.

Neuron, 1991 Sep, 7(3), 409 - 20
Localization of the hair cell's transduction channels at the hair bundle's top by iontophoretic application of a channel blocker; Jaramillo F et al.; In order to understand how the hair cell's mechanoelectrical transduction channels are gated during mechanical stimulation, it is essential to determine their location with respect to the hair bundle's constituent stereocilia . We localized the transduction channels by focally blocking receptor currents with iontophoretically ejected gentamicin, an aminoglycoside antibiotic that acts as a reversible channel blocker . The drug was most effective when directed at the top of a hair bundle, whereas application at the bundle's bottom or at the cuticular plate had little or no effect . Computer simulations of blocking agreed with experimental data only when the transduction channels were hypothesized to occur near the bundle's top . These results confirm that the hair cell's transduction channels are located near the stereociliary tips.

Mol Cell Biol, 1991 Sep, 11(9), 4616 - 26
Antifungal properties of the immunosuppressant FK-506: identification of an FK-506-responsive yeast gene distinct from FKB1; Brizuela L et al.; FK-506 is a novel and potent antagonist of T-cell activation and an inhibitor of fungal growth . Its immunosuppressive activity can be antagonized by the structurally related antibiotic rapamycin, and both compounds interact with cytoplasmic FK-506-binding proteins (FKBPs) in T cells and yeast cells . In this paper, we show that FK-506 and two analogs inhibit vegetative growth of Saccharomyces cerevisiae in a fashion that parallels the immunosuppressive activity of these compounds . Yeast mutants resistant to FK-506 were isolated, and at least three complementation groups (fkr1, fkr2, and fkr3) were defined . These fkr mutants show no alteration in their levels of FK-506-binding activity . Likewise, strains carrying null alleles of FKB1 (the yeast gene coding for the FKBP) remain FK-506 sensitive, indicating that depletion of yeast FKBP is not sufficient to confer an FK-506 resistance phenotype, although fkb1 null mutants are resistant to rapamycin . FKB1 does not map to the three fkr loci defined here . These results suggest that yeast FKBP mediates the inhibitory effect of rapamycin but that at least one other protein is directly involved in mediating the activity of FK-506 . Interestingly, the ability of FK-506 to rescue a temperature-sensitive growth defect of the fkr3 mutant suggests that the FKR3 gene may define such a protein.

Surg Laparosc Endosc, 1991 Sep, 1(3), 156 - 61
Does intraoperative gallbladder perforation influence the early outcome of laparoscopic cholecystectomy?
Soper NJ, Dunnegan DL.
Laparoscopic cholecystectomy is rapidly becoming the preferred therapy for symptomatic cholelithiasis . It was our impression that the necessary traction exerted on the gallbladder during this procedure would frequently lead to intraoperative perforation with bile leak . We sought to determine prospectively the incidence of gallbladder perforation during laparoscopic cholecystectomy and to ascertain whether or not intraoperative bile leak resulted in overt complications . Laparoscopic cholecystectomy was performed successfully on 250 patients between November 1989 and December 1990 . Gallbladder perforation occurred in 80 patients (32%) . Compared with those without a bile leak, there was a larger percentage of men (p < 0.05), and the average weight was greater (p < 0.01) in those developing a bile leak . Operating time was significantly longer in patients with gallbladder perforation (mean +/- SEM, 104 +/- 4 min) than in those without a bile leak (94 +/- 3 min, p < 0.01), presumably because of the increased time spent irrigating the abdomen and retrieving gallstones . There was no difference in postoperative serum liver enzymes, amount or type of analgesia administered, interval to return to work or to full activity, or the development of postoperative infections . A wound infection requiring antibiotic therapy developed in only one patient who had not suffered a bile leak . The incidence of bile leak during the performance of laparoscopic cholecystectomy is therefore appreciable, occurring in approximately a third of our patients . Gallbladder perforation does not lead to any other adverse complications and should not cause the surgeon to convert to an open cholecystectomy.

J Pediatr Surg, 1991 Sep, 26(9), 1067 - 9
Obstructing endobronchial fibrous histiocytoma: potential for lung salvage; Tagge E et al.; In the past 10 years two children, ages 3 1/2 and 7 years, have been seen with central endobronchial fibrous histiocytoma causing complete atelectasis . Each child had a 4- to 6-month history of cough, dyspnea and fever . After antibiotic failure, x-rays demonstrated complete unilateral lung collapse . Bronchoscopy in case 1 demonstrated total occlusion of the left mainstem bronchus with 80% stenosis of the right . Left pneumonectomy was ultimately performed with removal of tumor frm the right bronchus . Ten years later the patient is well . Case 2 had an extrinsic etiology ruled out by computed tomography scan . Ventilation/perfusion scan showed no ventilation and only faint perfusion of the involved lung . Pulmonary function testing showed moderate to severe restrictive changes with air trapping . Total obliteration of the left mainstem with tumor projecting into the carina was observed on bronchoscopy . Endoscopic resection was not felt to be safe . Thoracotomy showed a totally atelectatic, edematous lung filled with pus . The left main bronchus was opened, the tumor removed, and the distal bronchus lavaged and selectively ventilated . Partial lung expansion was obtained . The child is well 1 1/2 years later with a normal chest radiograph, pulmonary function tests, and bronchoscopy . Fibrous histiocytomas of the lung, if in a central endobronchial location, can cause complete lung collapse . A combination of tumor resection, lavage, and selective ventilation should be attempted as an alternative to pneumonectomy, even if the lung appears to be nonsalvageable.

Gan To Kagaku Ryoho, 1991 Sep, 18(12), 2121 - 7
{Intrapleural administration of pirarubicin in the treatment of malignant pleural effusion}; Gotoh T et al.; Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion . The dose of pirarubicin was 40 mg or 80 mg/body . All 15 patients were evaluable for both efficacy and toxicity . Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses . Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases . As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed . Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever . Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group . Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4) . Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.

Fortschr Med, 1991 Aug 20, 109(24), 473 - 5
{Chlamydia infection . A common, usually mild, infection with often severe consequences}; Petersen EE; Today, chlamydiae are among the most frequently sexually transmitted organisms . At least 5 to 10% of young, sexually active adults, will have a florid chlamydial infection . On account of its chronic nature, the paucity of symptoms, and the difficulty in diagnosing it, this infection is still underdiagnosed . The spectrum of the manifested pathologies range from genital to abdominal lesions, to conjunctivitis, pneumonia and arthritis . On account of the specific intracellular reproduction cycle, antibiotic therapy is not always able to completely clear up the infection . Today, chlamydial infection is the most common cause of infection-related sterility . During parturition, the neonate is often infected, with subsequent chronicity and sequelae.

Biochemistry, 1991 Aug 20, 30(33), 8216 - 22
Intramolecular semiquinone disproportionation in DNA . Pulse radiolysis study of the one-electron reduction of daunorubicin intercalated in DNA; Houee-Levin C et al.; The one-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants . The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 x 10(8) mol-1.dm3.s-1) in a way entirely consistent with a simple competition between .COO- disproportionation and the drug reduction . The semiquinone drug disappears by a first-order reaction (k = 1340 s-1) producing the hydroquinone form . This reaction leads to an equilibrium similar to the one without DNA and the equilibrium constant is very close to its value free in water (Kc approximately 25) . In addition, the stoichiometry of the first-order reaction is the one of a dismutation process . Therefore, it appears that the disproportionation occurs along an intramolecular path across DNA . This migration takes place under our experimental conditions, over a distance of ca . 100 base pairs, with a mobility of ca . 4.4 X 10(-11) m2.V-1.s-1, similar in magnitude to an excess electron mobility in doped organic polymers.

FEBS Lett, 1991 Aug 19, 288(1-2), 237 - 40
Characterization of the interaction of doxorubicin with (poly)phosphoinositides in model systems . Evidence for specific interaction with phosphatidylinositol-monophosphate and -diphosphate; de Wolf FA et al.; The anticancer drug doxorubicin penetrates into Langmuir monolayers containing phosphoinositides . Upon binding of doxorubicin to phosphoinositide-containing SUV, its fluorescence is self-quenched due to self-association . As compared to other anionic phospholipids, as much as 2- to 3-fold larger effects were obtained with PIP and PIP2, in mixtures of these lipids with DOPC . Doxorubicin competes efficiently with the non-penetrating antibiotic neomycin for binding to PIP2 . According to its penetration, specific binding of doxorubicin was half-maximal at 5-15 microM . It is likely that also in biological membranes doxorubicin binds specifically to PIP and PIP2.

Ann Thorac Surg, 1991 Aug, 52(2), 294 - 5
Neonatal pneumonectomy for isolated unilateral pulmonary artery agenesis; Canver CC et al.; A 23-day-old female newborn was evaluated for acyanotic respiratory distress immediately after birth . Echocardiogram and cardiac catheterization revealed absence of the right pulmonary artery . Subsequent course was complicated by necrotizing bronchopneumonia . Despite antibiotic therapy and ventilator support she failed to improve; right pneumonectomy was performed to remove the source of sepsis . This case represents an example in which an infectious complication in a rare congenital pulmonary malformation served as an indication for neonatal pneumonectomy.

Schweiz Med Wochenschr, 1991 Aug 6, 121(31-32), 1120 - 6
{Aseptic meningitis in pediatrics}; Etter CG et al.; We analyzed the 259 pediatric patients (69% males, 31% females) treated for aseptic meningitis at the Department of Pediatrics (Inselspital), University of Berne, Switzerland, during the 10-year period from 1978 to 1987 . 79% were in- and 21% outpatients . The main study purpose was the evaluation of clinical presentation, diagnostic workup, course and prognosis of this disease entity . The clinical characteristics (fever, meningitic signs, headache, nausea and vomiting, and usually normal consciousness) were not discriminative for differential diagnosis . On the other hand, pleocytosis in cerebrospinal fluid averaged 406 x 10(6) cells/l (57% mononuclear cells) at first lumbar puncture, and 6 to 12 hours later showed both slight decrease of total cell count and clear shift to mononuclear cells (71%) . The course of the disease was always short and benign . Complications, usually of a neurologic nature, occurred in only 10% and all were mild and reversible . Nevertheless, follow-up interview by phone identified 21% of patients with transient post-meningitic disorders, especially prolonged episodes of stress-induced headache . However, except for one case of chronic hydrocephalus, there were no severe or persistent sequelae . Neither complications nor sequelae correlated with patient age or laboratory findings . Our results confirm that aseptic meningitis in children is relatively benign, and underline the importance of rest and relaxation during convalescence . Rapid, reliable and cheap viral diagnostic tests in the cerebrospinal fluid could simplify the management of the individual patient with regard to repeated lumbar punctures (in 36%), surveillance in the hospital (in 79%), and antibiotic therapy (in 25%).

Biochim Biophys Acta, 1991 Aug 6, 1074(3), 433 - 8
Enkephalin hydrolysis by human serum biotinidase; Oizumi J et al.; Purified human serum biotinidase exhibited amino-exo-peptidase activity . Enkephalins and dynorphin A (less than 10-mer) seemed to be the most appropriate substrates among various physiological peptides in terms of the kcat/Km values . Similar kcat/Km values were obtained for both biocytin (biotinyllysine) and these opioid-neuropeptides . Neuro-oligo-peptides ranging from 2-mer to 18-mer were hydrolyzed . The presence of amino group at the carboxyl terminal position increased the kcat/Km value by decreasing the Km value . The results of inhibition studies using various kinds of antibiotic inhibitors, metals, and chelating agents indicated that enkephalin hydrolysis was mediated by the peptide-hydrolyzing center probably containing Zn ions . This aminopeptidase activity was uniquely inhibited by a vitamin of biocytin . The reason for the high content of biotinidase activity in serum may be related to the binary function of this enzyme; i.e., biocytin hydrolyzing amidase and enkephalin hydrolyzing aminopeptidase functions.

EMBO J, 1991 Aug, 10(8), 1989 - 95
Protein import into Escherichia coli: colicins A and E1 interact with a component of their translocation system; Benedetti H et al.; Colicins are antibiotic proteins that kill sensitive Escherichia coli cells . Their mode of action involves three steps: binding to specific receptors located in the outer membrane, translocation across this membrane, and action on their targets . A specific colicin domain can be assigned to each of these steps . Colicins have been subdivided into two groups (A and B) depending on the proteins required for them to cross the external membrane . Plasmids were constructed which led to an overproduction of the Tol proteins involved in the import of group A colicins . In vitro binding of overexpressed Tol proteins to either Tol-dependent (group A) or TonB-dependent (group B) colicins was analyzed . The Tol dependent colicins A and E1 were able to interact with TolA but the TonB dependent colicin B was not . The C-terminal region of TolA, which is necessary for colicin uptake, was also found to be necessary for colicin A and E1 binding to occur . Furthermore, only the isolated N-terminal domain of colicin A, which is involved in the translocation step, was found to bind to TolA . These results demonstrate the existence of a correlation between the ability of group A colicins to translocate and their in vitro binding to TolA protein, suggesting that these interactions might be part of the colicin import process.

J Public Health Med, 1991 Aug, 13(3), 214 - 8
An unusual community outbreak of influenza A; Mitchell E et al.; The Hong Kong H3N2 subtype of influenza A virus appeared in 1968 and since then has caused epidemics of varying degrees of severity . We describe a community outbreak of influenza A H3N2 which occurred in members of a bowls club in an English rural village in late April 1989 . The explosive onset, high attack rate (34/41 = 83 per cent) in those exposed, and the clinical presentation initially suggested a toxic or allergic aetiology . Twenty-three persons consulted their general practitioners; before the diagnosis was made all cases were considered to merit antibiotic therapy and 17/23 were prescribed steroids or bronchodilators on account of persisting severe wheeze and chest tightness . One of the 23 was admitted to hospital . There were no deaths . Influenza vaccination is recommended for people at special risk but protective efficacy is relatively low and short-lived . Only two of the group had received influenza vaccination since the beginning of October 1988 and both became symptomatic . The use of amantadine for the prevention and early treatment of influenza A in selected situations merits serious consideration, provided the diagnosis is made sufficiently early.

Zh Mikrobiol Epidemiol Immunobiol, 1991 Aug, (8), 68 - 71
{The functional activity of the macrophages in experimental intestinal dysbacteriosis in rats}; Zaitseva LG et al.; The study of the functional activity of macrophages in the peritoneal exudate and spleen of Sprague-Dawley rats was made under the conditions of dysbacteriosis caused by the administration of antibiotics (gentamicin and phenoxymethylpenicillin) and short-term food deprivation . The complex study of the key functions of macrophages, carried out on the same pool of cells, showed that under the conditions of antibiotic therapy the enhanced function of ingestion was accompanied by a decrease in all other investigated functional parameters of peritoneal macrophages: the intensity of protein synthesis, oxidation metabolism, the activity of lysosomal apparatus, 5'-nucleotide activity . In contrast to changes observed in macrophages after the administration of antibiotics, short-term food deprivation induced increased functional activity as shown by most tests used in this investigation (such as tests for the ingestion of sheep red blood cells, 51Cr, nitro blue tetrazolium, acridine orange, 5'-nucleotidase activity), but did not affect the intensity of protein synthesis in macrophages . The comparison of these results with the data obtained by the authors after the administration of an immunomodulating agent made it possible to regard short-term food deprivation, judging by its effect on the functional activity on macrophages, as an immunostimulating action.

Khirurgiia (Mosk), 1991 Aug, (8), 136 - 8
{Treatment of acute hematogenous osteomyelitis in children}; Rusak PS et al.; Experience in treatment of 348 children with acute hematogenic osteomyelitis is analysed . Newborn infants and children whose ages ranged from 1 to 15 years formed a group of patients . Of decisive importance in the outcome of the disease are early diagnosis and emergency operative measures, aimed at decompressing, opening and cleansing the purulent foci, producing a high concentration of antibiotics in the focus . Children who are in a grave condition are subjected to short-term preoperative management for 3-4 hours for detoxification, improvement of hemodynamics, prevention of septic shock and hyperthermia . Antibiotic therapy is given in 3 stages: in the first 10 days no less than 3 antibiotics are injected into the veins, into the muscles, and into the bones; from days 11 to 20 2 antibiotics are injected intramuscularly or into the bone; in the next 10 days one antibiotic is administered into the bone or muscle . Newborns and infants received injections by daily intraosseous puncture during the first 8-10 days of treatment . It is shown that the results of treatment may be improved only by intensive and complex measures applied timely and urgently . The mortality rate was 1.7% for the decade and 0.8% for the last 2 years.

Curr Genet, 1991 Aug, 20(3), 211 - 8
Hygromycin- and paromomycin-resistant mutants of Aspergillus nidulans alter translational fidelity; Martinelli SD et al.; Mutants of Aspergillus nidulans resistant to the aminoglycoside antibiotics paromomycin and hygromycin B have been isolated and their growth characteristics are described here . Most paromomycin mutants were cross-resistant to hygromycin and geneticin . All the hygromycin-resistant mutants were slightly cross-resistant to geneticin . Out of the 15 mutants tested 14 had drug-resistant ribosomes in vitro and all 12 of those investigated further had reduced levels of translational misreading . Five new loci have been found--parA on linkage group I, hygA on III, hygB on IV, hygC on V, hygD on VI and parB on VIII . This increases, to at least 12, the number of translational fidelity loci in A . nidulans.

Antimicrob Agents Chemother, 1991 Aug, 35(8), 1591 - 5
Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor; Degenkolb J et al.; We used the Tn10-encoded Tet repressor, which has a highly specific binding capacity for tetracycline, to probe contacts between the drug and protein by chemical interference studies of the antibiotic . For that purpose, the equilibrium association constants of modified tetracyclines with the Tet repressor and Mg2+ cations were determined quantitatively . The results confirm the previous notion that Mg2+ probably binds with the oxygens at positions 11 and 12 and is absolutely required for protein-drug recognition . Modifications were introduced at positions seven, six, five, and four of the drug, and anhydrotetracycline was also studied . Substitutions or eliminations of functions at these positions influenced binding to the Tet repressor up to 35-fold . The introduction of an azido function at position seven in 7-azidotetracycline and epimerization of the substituents at position four in 4-epitetracycline lead to a 2- or 25-fold reduction, respectively, of Tet repressor affinity in those compounds . Anhydrotetracycline bound about 35-fold more strongly than tetracycline did, indicating that the oxygen at position 11 may be involved in Tet repressor recognition . This increased binding is in contrast to the lower antibiotic activity of anhydrotetracycline and indicates that the Tet repressor and ribosomes recognize the drug differently.

Pharm Res, 1991 Aug, 8(8), 979 - 88
Predicting fraction dose absorbed in humans using a macroscopic mass balance approach; Sinko PJ et al.; A theoretical approach for estimating fraction dose absorbed in humans has been developed based on a macroscopic mass balance that incorporates membrane permeability and solubility considerations . The macroscopic mass balance approach (MMBA) is a flow model approach that utilizes fundamental mass transfer theory for estimating the extent of absorption for passively as well as nonpassively absorbed drugs . The mass balance on a tube with steady input and a wall flux of Jw = PwCb results in the following expression for fraction dose absorbed, F: {formula; see text} where the absorption number, An = L/R.Pw/(vz), L and R are the intestinal length and radius, Pw is the unbiased drug wall permeability, (vz) is the axial fluid velocity, C*b = Cb/Co and is the dimensionless bulk or lumen drug concentration, Cb and Co are the bulk and initial drug concentrations, respectively, and z* is the fractional intestinal length and is equal to z/L . Three theoretical cases are considered: (I) Co less than or equal to S, Cm less than or equal to S, (II) Co greater than S, Cm less than or equal to S, and (III) Co greater than S, Cm greater than S, where S is the drug solubility and Cm is the outlet drug concentration . Solving the general steady-state mass balance result for fraction dose absorbed using the mixing tank (MT) and complete radial mixing (CRM) models results in the expressions for the fraction dose absorbed in humans . Two previously published empirical correlations for estimating fraction dose absorbed in humans are discussed and shown to follow as special cases of this theoretical approach . The MMBA is also applied to amoxicillin, a commonly prescribed orally absorbed beta-lactam antibiotic for several doses . The parameters used in the correlation were determined from in situ or in vitro experiments along with a calculated system scaling parameter . The fraction dose absorbed calculated using the MMBA is compared to human amoxicillin pharmacokinetic results from the literature with initial doses approximated to be both above and below its solubility . The results of the MMBA correlation are discussed with respect to the nonpassive absorption mechanism and solubility limitation of amoxicillin . The MMBA is shown to be a fundamental, theoretically based model for estimating fraction dose absorbed in humans from in situ and in vitro parameters from which previously published empirical correlations follow as special cases.

Jpn J Antibiot, 1991 Aug, 44(8), 899 - 911
{Clinical evaluation of imipenem/cilastatin sodium against severe infections complicating hematological disorders and solid tumors}; Saito H et al.; Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors . Fifty patients are included in the present analysis of efficacy and 64 in that of safety . 1 . Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5% . Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2% . 2 . For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors . 3 . The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders . The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0% . 4 . For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9% . 5 . Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients . However, they were mild and disappeared after discontinuation of this drug . From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors.

J Antibiot (Tokyo), 1991 Aug, 44(8), 885 - 94
Naphthyridinomycin-DNA adducts: a molecular modeling study; Cox MB et al.; Monocovalent groove binding complexes of antitumor antibiotic naphthyridinomycin and its analogs with DNA sequence d(ATGCAT)2 have been studied by molecular mechanics to understand which enantiomer of the drug and what chirality at C(7) of the drug are preferred for forming better drug-DNA adducts . The effect of hydroquinone intermediate and the substitution at C(11) on drug-DNA interactions have also been investigated . The results indicate that the enantiomer that forms the best adduct is different from the one reported earlier in the literature . The drug with an R configuration at C(7) is preferred for binding . The hydroquinone models do not necessarily provide a given analog of the drug with additional favorable DNA interactions . The substitution at C(11) by OH provides the best binding model . This finding agrees well with the results from previous biochemical studies . The sequence specific studies indicate that the sequence d(ATGCAT)2 is slightly preferred over others.

J Antibiot (Tokyo), 1991 Aug, 44(8), 838 - 43
The structure of heneicomycin; Dewey RS et al.; The antibiotic heneicomycin (1), C44H62N2O11, was isolated from cultures of Streptomyces filipinensis as an amorphous yellow powder . Mass spectral and NMR analysis showed the compound to be a deoxy modification of aurodox (2), a member of the elfamycin antibiotic family . A marked change in mass spectral fragmentation compared to aurodox and 1H NMR couplings indicated the absence of the hydroxyl at position 30 of aurodox (position 3 of the tetrahydropyran).

J Med Microbiol, 1991 Aug, 35(2), 98 - 102
Detection of Borrelia burgdorferi in cerebrospinal fluid by the polymerase chain reaction; Kruger WH et al.; The polymerase chain reaction (PCR) was used to amplify specific DNA sequences from different clinical isolates of Borrelia burgdorferi and from cerebrospinal fluid (CSF) of two patients with Lyme disease of the central nervous system . The amplification products were separated by polyacrylamide gel electrophoresis and visualised by ethidium bromide staining . The definitive identification of amplified DNA as a part of the B . burgdorferi flagellin gene was achieved by hybridisation to a 40-base oligonucleotide probe complementary to a part of the spirochaetal gene but not to the primers . Attempts to cultivate borreliae from either patient were unsuccessful and one patient had no serological marker in serum or CSF to indicate borreliosis . Clinical symptoms of both patients regressed with antibiotic therapy . The PCR system is a powerful and rapid technique to amplify flagellin gene sequences from CSF of patients with neuroborreliosis . Only one-tenth of the time needed for cultivation was required from CSF sampling to diagnosis . Gene amplification might, for the first time, allow effective monitoring of therapy for patients with Lyme disease of the central nervous system.

Am J Physiol, 1991 Aug, 261(2 Pt 1), L218 - 21
Method for rapid evaluation of topically applied agents to cystic fibrosis airways; Wine JJ et al.; The proposal is to target a single maxillary sinus for treatment with agents designed to reverse or ameliorate the cystic fibrosis (CF) defect in airway mucosa, with the opposite sinus serving as a control . Selected CF patients have undergone maxillary antrostomy and antibiotic lavage to help relieve severe pulmonary disease and chronically impacted and infected sinuses . After treatment, the mucosa in the maxillary sinuses of these patients are accessible and can be bathed with fluids introduced via the stomas with procedures that restrict the fluid to a single sinus . The ability of an agent to reverse mucosal pathology can therefore be determined easily with the mucosa of the contralateral sinus serving as a control . Electrophysiological properties, amounts and composition of fluid and mucus, immune functions, and bacterial colonization can be measured accurately and repeatedly . The consistent observation that sinus involvement in CF is near universal and bilaterally symmetric offers a unique opportunity for a simultaneous within-subject, double-blinded control paradigm . This approach should speed evaluation of any agent designed to improve airway mucosal function.

Postgrad Med, 1991 Aug, 90(2), 241 - 4, 247-8
Drug-induced renal toxicity . Help in recognizing offending agents; Farrugia E et al.; Drug-induced kidney disease is common, especially in hospitalized patients, and prompt recognition of the various nephrotoxic syndromes is important because many are reversible . Risk factors should be assessed before patients are given an agent that may cause acute renal failure (eg, nonsteroidal anti-inflammatory drug, aminoglycoside antibiotic, angiotensin-converting enzyme inhibitor, radiocontrast agent) . Discontinuation of the responsible drug is often the only necessary therapy.

Arthritis Rheum, 1991 Aug, 34(8), 1056 - 60
Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy; Schoen RT et al.; Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period . Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup . The remaining 4 patients (20%) had persistent or recurrent synovitis . We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.

Pol Arch Med Wewn, 1991 Aug, 86(2), 75 - 83
{Infectious aortic valve endocarditis . Echocardiographic evaluation}; Hlawaty M et al.; In the group of 37 patients (pts) with infective endocarditis of aortic valve comparative analysis of echocardiograms with intraoperative or pathomorphological findings was performed . Infection caused development of vegetations in 17 pts, cusp rupture in 7 and perivalvular abscess in 4 pts . Echocardiographic examination enabled diagnosis of vegetations in 16 pts . In 2 pts abscess cavity was shown between mitral and aortic annulus . Two-dimensional echocardiography provided more detailed data concerning number and localization of vegetation, and development of perivalvular abscess cavity . However cusps rupture was shown by M-mode echograms in 4 from 7 pts . In the course of antibiotic therapy 7 pts died: from 30 pts treated surgically the result of treatment was beneficial in 27 . The examinations confirmed poor clinical prognosis of premature mitral valve closure for the patients with aortic insufficiency.

Fundam Appl Toxicol, 1991 Aug, 17(2), 335 - 46
Comparative toxicity and carcinogenicity studies of tetracycline and oxytetracycline in rats and mice; Dietz DD et al.; Two-year toxicity and carcinogenicity studies of oxytetracycline hydrochloride and tetracycline hydrochloride, two structurally similar and widely used antibiotics, were performed in F344/N rats and B6C3F1 mice . Rats and mice were continuously exposed via their diet to the following levels of antibiotic: oxytetracycline HCl--rats 0, 25,000, or 50,000 ppm; mice 0,6,300, or 12,500 ppm; tetracycline HCl--rats and mice 0, 12,500, or 25,000 ppm . On a milligram per kilogram of body weight basis these exposures represent doses that are 20 to 140 times daily human therapeutic doses . Dose-related increased survival was noted among oxytetracycline-treated male rats and tetracycline-treated female rats and male mice, while treatment-related reduced body weight gain occurred in oxytetracycline- and tetracycline-treated mice . Microscopic changes included fatty metamorphosis and focal cellular change in livers of oxytetracycline-treated male rats and basophilic cytoplasmic and clear cell change in livers of tetracycline-treated male rats . The only neoplastic changes were a marginally increased trend in pheochromocytoma of the adrenal medulla (equivocal evidence only) among oxytetracycline-exposed male rats (12/50 controls, 19/50 low dose, 24/50 high dose) and an increased incidence of pituitary adenoma or adenocarcinoma among high-dose oxytetracycline-treated female rats (20/50 controls, 32/50 high dose) . Although oxytetracycline and tetracycline appeared to increase the incidence of pituitary hyperplasia in high-dose male and female rats, respectively, the total incidence of proliferative changes (hyperplasia, adenoma, and adenocarcinoma) was not affected by antibiotic exposure . The results from these studies therefore support the notion that neither antibiotic is carcinogenic in rodents . There were several negative trends suggesting possible protective effects by both these tetracycline analogs against certain spontaneous neoplastic and non-neoplastic changes.

Antibiot Khimioter, 1991 Aug, 36(8), 42 - 4
{Mathematical modeling of ampicillin pharmacokinetics in patients with altered excretory function of the kidneys}; Manuilov KK; A physiological model of ampicillin pharmacokinetics in man is proposed . Its design stems from the data characterizing the antibiotic distribution in rats . The model is useful in describing the pharmacokinetics of ampicillin after its intravenous and intramuscular administration . An adequate description of the antibiotic distribution in blood suggested an agreement with the real values of the estimated antibiotic concentrations in the tissues . The concentrations of ampicillin and sulbactam in the tissues after their intramuscular combined administration in doses of 1 and 0.5 g, respectively, were compared . The physiological model of the pharmacokinetics was applied to evaluation of a possible interval in changing of the antibiotic half-life . There was analytical relationship between the ampicillin half-life and efficiency of the renal function.

Neurol Med Chir (Tokyo), 1991 Aug, 31(8), 508 - 13
Clinicopathological study of bacterial intracranial aneurysms; Takeshita M et al.; The authors report the clinicopathological findings in six cases of bacterial intracranial aneurysms . All patients received appropriate high-dose antibiotics, and four were treated surgically . One patient with multiple aneurysms of the main trunks died of disseminated intravascular coagulation . Autopsy disclosed no apparent aneurysm or inflammatory cell infiltration, but a partially interrupted internal elastic lamina and thickened intima were disclosed at the angiographical aneurysm sites . These findings suggest that 1) appropriate high-dose antibiotics are effective against inoperable bacterial aneurysms in the main trunks, 2) new aneurysms may be formed in patients with cyanotic congenital heart disease, because bacterial emboli can directly reach the cerebral circulation and reimplant on the fragile arterial walls after vasculitis . Histological examination of aneurysmal walls revealed inflammatory cell infiltration after resolution of clinical endocarditis . This suggests that both appropriate high-dose antibiotic therapy and surgery should be considered in patients with distal bacterial aneurysms.

AIDS Res Hum Retroviruses, 1991 Aug, 7(8), 707 - 12
Brefeldin A inhibits the processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1; Pal R et al.; The processing and secretion of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected T cells and in primary macrophages treated with an antiviral antibiotic brefeldin A (BFA) . BFA blocks the egress of proteins from the endoplasmic reticulum and has a profound effect on the structure of cis/medial Golgi . In MOLT-3 cells infected with the IIIB strain of HIV-1 (MOLT-3/IIIB), BFA inhibited the intracellular processing of gp160 . The secretion of envelope proteins from these cells was significantly inhibited in the presence of BFA . The gag proteins, on the other hand, were processed and secreted normally . BFA also inhibited the proteolytic processing of gp160 in primary macrophages infected with HIV-1 . The infectivity of virus pelleted from the medium of MOLT-3/IIIB cells treated with BFA was markedly lower than that obtained from untreated cells . These results demonstrate that the proteolytic processing of gp160 in HIV-1-infected cells takes place after the glycoprotein exists the endoplasmic reticulum and that the transport of glycoprotein to the cell surface is required for assembly of complete HIV-1 particles.

EMBO J, 1991 Aug, 10(8), 2203 - 14
A functional pseudoknot in 16S ribosomal RNA; Powers T et al.; Several lines of evidence indicate that the universally conserved 530 loop of 16S ribosomal RNA plays a crucial role in translation, related to the binding of tRNA to the ribosomal A site . Based upon limited phylogenetic sequence variation, Woese and Gutell (1989) have proposed that residues 524-526 in the 530 hairpin loop are base paired with residues 505-507 in an adjoining bulge loop, suggesting that this region of 16S rRNA folds into a pseudoknot structure . Here, we demonstrate that Watson-Crick interactions between these nucleotides are essential for ribosomal function . Moreover, we find that certain mild perturbations of the structure, for example, creation of G-U wobble pairs, generate resistance to streptomycin, an antibiotic known to interfere with the decoding process . Chemical probing of mutant ribosomes from streptomycin-resistant cells shows that the mutant ribosomes have a reduced affinity for streptomycin, even though streptomycin is thought to interact with a site on the 30S subunit that is distinct from the 530 region . Data from earlier in vitro assembly studies suggest that the pseudoknot structure is stabilized by ribosomal protein S12, mutations in which have long been known to confer streptomycin resistance and dependence.

J Gen Virol, 1991 Aug, 72 ( Pt 8), 1953 - 8
Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines; Simmer B et al.; Herpesvirus (h.) saimiri, an infectious agent of squirrel monkeys, is capable of persisting in T lymphocytes of various primate species . It has been used as a vector for the functional analysis of regulatory genes in primary human T lymphocytes . As it is not yet known whether other cell types are capable of supporting viral persistence, various human cell lines were investigated using selectable h . saimiri recombinants . The lines chosen represent cells from the epithelium and connective tissue as well as from all haematopoietic lineages, i.e . cells of B and T lymphoid origin as well as myeloid-, fibroblast- and carcinoma-derived cultures converted to Geneticin or hygromycin B resistance, and harbouring episomal DNA of the selectable recombinants . The Burkitt's lymphoma-derived cell line Raji also contained simultaneously persisting episomes of the Epstein-Barr virus . Most of the cell cultures except a pancreatic carcinoma line and foreskin fibroblasts did not produce infectious virus . These observations show that a herpesvirus genome can persist episomally in a broad range of cultured cell types . The variety of infectable cell types and species suggests the presence of a widely distributed and well conserved virus receptor for h . saimiri . Thus the h . saimiri genome could be applied more generally as a vector.

Gan To Kagaku Ryoho, 1991 Aug, 18(10), 1677 - 80
{Study on the intra-tumor tissue concentration of zinostatin stimalamer in the liver following intra-arterial injection of zinostatin stimalamer (YM881) suspension}; Toge T et al.; A suspension of zinostatin stimalamer (YM881), an antitumor protein antibiotic in iodized poppy oil-fatty acid ester, was injected into the hepatic artery of 2 patients who received surgical treatment of hepatic tumors . Single doses of 4 mg of zinostatin stimalamer were injected into the hepatic artery by Seldinger's method . Two and 4 weeks after the dose, tissue samples were collected from the tumor and non-tumor regions close to and distant (normal tissues) from the tumor, and zinostatin stimalamer concentrations in these tissues were assayed by RIA . In one of the two patients, plasma concentrations of the drug were also assayed . Concentrations of zinostatin stimalamer in the tumor tissues (381.8 ng/g) were about 55 times greater than those in the normal tissue (6.9 ng/g) in patient No . 1 (week 4), and about 17 times in patients No . 2 (13.9 ng/g in the normal tissue and 229.8 ng/g in the tumor tissues in week 2) . Plasma concentrations were assayed in patient No . 2, and were 510.3 ng/ml after one hr., 385.3 ng/ml after 3 hrs., 184.4 ng/ml after 6 hrs., and 45.4 ng/ml after 24 hrs., with a half life of 7.1 hrs . These results indicate that zinostatin stimalamer suspended in iodized poppy oil fatty acid ester persisted in the hepatic tumor tissues at the high concentrations, when injected into the hepatic artery, but was eliminated fairly rapidly from the plasma.

J Bacteriol, 1991 Aug, 173(16), 5060 - 7
Tn4563 transposition in Streptomyces coelicolor and its application to isolation of new morphological mutants; Schauer AT et al.; The Tn3-like transposon Tn4556 (and its derivatives Tn4560 and Tn4563) has been used for insertion mapping of genetic loci cloned on plasmids, but it has been difficult to obtain chromosomal insertions, largely because of the lack of a strong selection against transposon donor molecules . In this communication, we report two efficient selection techniques for transposition and their use in the isolation of chromosomal insertion mutations . A number of independent Streptomyces coelicolor morphological mutants (bld and whi) were obtained . Two of the bld mutations were mapped to locations on the chromosome by SCP1-mediated conjugation; at least one mutation, bld-5m1, appears to define a novel locus involved in control of S . coelicolor morphogenesis and antibiotic production.

Biochemistry, 1991 Jul 23, 30(29), 7271 - 6
A fluorescence lifetime study of virginiamycin S using multifrequency phase fluorometry; Clays K et al.; Using multifrequency phase fluorometry, fluorescence lifetimes have been assigned to the different protolytic forms of the antibiotic virginiamycin S . These lifetimes are 0.476 +/- 0.005 ns for the uncharged form, 1.28 +/- 0.2 and 7.4 +/- 0.2 ns for the zwitterionic form, 1.19 +/- 0.01 ns for the negatively charged form, and 1.9 +/- 0.1 ns for the double negatively charged form . The assignments are based on lifetime measurements as a function of pH, volume percent ethanol, and excitation wavelength . Excited-state proton transfer is taken into account . It is complete at pH values lower than 1, and no fluorescence of the fully protonated charged form is observed . At pH 8, an excited-state pK* increase is calculated, but proton association is too slow to cause excited-state proton transfer . The addition of divalent cations, at pH 9.4, increases the lifetime of the negatively charged form to a value dependent upon the specific nature of the cation (7.58 +/- 0.06 ns for Mg2+, 6.54 +/- 0.02 ns for Ca2+, and 3.74 +/- 0.05 ns for Ba2+) . Monovalent cations do not influence the lifetimes, indicating that their binding to the macrocycle does not influence the fluorescent moiety . The model compound 3-hydroxypicolinamide shows an analogous behavior, but the retrieved lifetime can differ significantly.

Pol Tyg Lek, 1991 Jul 22-28, 46(30-31), 565 - 7
{Post-traumatic infections of the musculoskeletal locomotor system; prophylaxis and treatment}; Szulc W et al.; An analysis of epidemiology of the post-traumatic infections of the locomotive system, prophylaxis and treatment in presented . Infections are the most severe complications of the open bone fractures and orthopedic surgery . An incident of inflammatory complications following the open bone fractures is very high (20% according to Burrie) . An incidence of complications following orthopedic surgeries is somewhat lower--0.2-9.0% . Within 1976-1986, as much as 585 patients with chronic osteitis, including 222 patients with post-traumatic infections, were treated at the Department of Orthopedic Surgery, Medical Academy in Warsaw . Therapy depended on the general and local health status, and the types of surgery were diversified . The treatment included, first of all, radical removal of crushed and necrotic tissues, stabilization of the fractured bone fragments with the external stabilizer, AO plate or the Polish original method of the stable internal osteosynthesis--ZESPOL, decompression of the crack with the aid of permanent flow or suction drainage, systemic or local antibiotic therapy, administration of vasodilating agents, and the primary skin plasty in some cases.

N Engl J Med, 1991 Jul 18, 325(3), 159 - 63
The long-term course of Lyme arthritis in children; Szer IS et al.; BACKGROUND AND METHODS . The natural history of Lyme disease is not completely known . We studied the long-term course of Lyme arthritis in 46 children in whom the onset of the disease occurred between 1976 and 1979 and who received no antibiotic therapy for at least the first four years of the illness . RESULTS . Of the 46 children (age range, 2 to 15 years), 33 (72 percent) initially had erythema migrans, 7 (15 percent) had influenza-like symptoms, and 6 (13 percent) had migratory joint pain . These manifestations were followed by brief attacks of arthritis, particularly affecting the knee . The percentage of children with recurrent episodes of arthritis declined each year . By year 4, only 10 children still had a mean of two episodes of arthritis per year; the duration of arthritis was generally longer in older children (P less than 0.05) . During the sixth year of illness, two children (4 percent) had keratitis, and more than 10 years after the onset of disease, a subtle encephalopathy developed in two other children . Of the 39 children whom we were able to contact in 1988-1989, 12 (31 percent) still had occasional brief episodes of joint pain and 1 (3 percent) had marked fatigue . All 46 children had positive IgG antibody responses to Borrelia burgdorferi throughout the illness and on long-term follow-up . As compared with those who became asymptomatic, the children with recurrent symptoms more often had IgM responses to the spirochete and had significantly higher IgG titers (P less than 0.05) . CONCLUSIONS . The course of initially untreated Lyme disease in children may include acute infection followed by attacks of arthritis and then by keratitis, subtle joint pain, or chronic encephalopathy.

Eur J Biochem, 1991 Jul 15, 199(2), 411 - 5
Prepeptide sequence of cinnamycin (Ro 09-0198): the first structural gene of a duramycin-type lantibiotic; Kaletta C et al.; The tetracyclic polypeptide antibiotic cinnamycin (Ro 90-0198) belongs to the duramycin-type lantibiotics and contains the unusual amino acids threo-3-methyl-lanthionine, meso-lanthionine, lysinoalanine and 3-hydroxyaspartic acid . Its structural gene, referred to as cinA, has been identified on isolated chromosomal DNA of the Ro 09-0198-producing strain Streptoverticillium griseoverticillatum via a 39-residue oligonucleotide probe derived from fragment 7-19 of the hypothetical prolantibiotic sequence CRQSCSFGPFTFVCDGNTK . This propeptide part was then found within an open reading frame of 77 amino acids . In contrast to the nisin-type prelantibiotics, this first duramycin-type prelantibiotic has an unusually long leader sequence of 58 amino acids . it also differs in the processing site and the direction of the formation of the threo-3-methyl-lanthionine bridges is from N-terminal cysteine to C-terminal dehydrated threonine residues, whereas the meso-lanthionine and lysinoalanine bridges are formed by addition reactions from C-terminal cysteine or lysine to N-terminal dehyrated serine residues.

Med J Aust, 1991 Jul 15, 155(2), 122 - 3
Beneficial effects of hyperbaric oxygen therapy in Nocardia brasiliensis soft-tissue infection; Walker RM et al.; OBJECTIVE: To report the success of hyperbaric oxygen therapy in the treatment of Nocardia brasiliensis mycetoma . We believe this to be only the second report in the medical literature of hyperbaric oxygen therapy used in the therapy of nocardial disease . CLINICAL FEATURES: A 78-year-old man presented to a general hospital outpatient clinic after eight months with a painless swollen left foot . There was no significant medical history, no trauma had occurred, and no foreign body had been detected . The dorsum of the foot had a discharging sinus, from which N . brasiliensis was isolated . INTERVENTIONS: After unsuccessful treatment with surgical debridement and high-dose antibiotic therapy, hyperbaric oxygen therapy was administered in a multiplace recompression chamber (one hour of treatment at 1.8 atmospheres absolute followed by a 30 minute "ascent" to surface pressure) . A total of 19 treatments were administered . OUTCOME: Successful healing of an N . brasiliensis mycetoma of the left foot . CONCLUSION: In this case of N . brasiliensis mycetoma involving the lower extremity, the conventional management of surgery and antibiotic therapy was unsuccessful, and only with the addition of hyperbaric oxygen therapy did clinical recovery occur.

Med J Aust, 1991 Jul 15, 155(2), 128 - 9
Hypernatraemic dehydration after Lucozade; Bucens IK et al.; OBJECTIVE: To emphasise the dangers of inappropriate rehydration fluids in the treatment of gastroenteritis . CLINICAL FEATURES: A two-year-old girl was admitted to hospital in shock and unconscious . She had a 36-hour history of diarrhoeal illness and had received Lucozade . Therapy with this hypertonic fluid resulted in worsening diarrhoea and seizures . On examination she had hypernatraemic dehydration and decorticate posturing . INTERVENTION AND OUTCOME: An intravenous line was inserted, stable plasma protein solution was given, and she was admitted to the intensive care unit . Anticonvulsant and antibiotic therapy were begun . Significant neurological impairment was still evident after 14 days, at which time shw was discharged from hospital . Six months later she had made a good recovery, with no persisting neurological deficit . CONCLUSION: The inappropriate use of hypertonic fluids in gastroenteritis may be associated with significant electrolyte imbalances and neurological sequelae.

J Clin Microbiol, 1991 Jul, 29(7), 1392 - 6
Seropositivity to Helicobacter pylori: lack of association with length of hospitalization; Thoene JG et al.; To examine the possibility of nosocomial spread of Helicobacter pylori, a serosurvey (n = 238) was conducted at Perry Point Department of Veterans Affairs Medical Center, an institution providing both acute and chronic care . We hypothesized that if significant nosocomial transmission was occurring, seropositivity (as measured by enzyme-linked immunosorbent assay {ELISA}) would correlate with length of stay in the facility . Whether treated as a continuous or dichotomous variable, the ELISA results did not correlate significantly with length of stay even after adjustments were made for age, race, antibiotic use, gastrointestinal instrumentation, and diagnoses by using multiple-regression models . Age was found to be a significant risk factor for a higher ELISA optical density value . A history of chronic obstructive pulmonary disease was significantly protective among internal medicine ward patients in adjusted analysis; black race was a significant risk factor among psychiatry ward patients . Our results confirm the association of H . pylori infection with age but provide no indication that extended hospitalization is a risk factor for infection.

Biochemistry, 1991 Jul 9, 30(27), 6705 - 10
Kirromycin drastically reduces the affinity of Escherichia coli elongation factor Tu for aminoacyl-tRNA; Abrahams JP et al.; We have studied the interaction between EF-Tu-GDP or EF-Tu-GTP in complex with kirromycin or aurodox (N1-methylkirromycin) and aminoacyl-tRNA, N-acetylaminoacyl-tRNA, or deacylated tRNA . Three independent methods were used: zone-interference gel electrophoresis, GTPase stimulation, and fluorescence . All three methods revealed that kirromycin induces a severe drop in the stability of the complex of EF-Tu-GTP and aminoacyl-tRNA of about 3 orders of magnitude . The affinities of EF-Tu-kirromycin-GTP and EF-Tu-kirromycin-GDP for aa-tRNA were found to be of about the same order of magnitude . We conclude that kirromycin and related compounds do not induce a so-called GTP-like conformation of EF-Tu with respect to tRNA binding . The findings shed new light on the mechanism of action of the antibiotic during the elongation cycle . In contrast to indirect evidence previously obtained in our laboratory {Van Noort et al . (1982) EMBO J . 1, 1199-1205; Van Noort et al . (1986) Proc . Natl . Acad . Sci . U.S.A . 71, 4910-4914}, we were unable to demonstrate complexes of EF-Tu-aurodox-GTP/GDP with N-acetylaminoacyl-tRNA or deacylated tRNA by direct detection using zone-interference gel electrophoresis . Modification with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) decreases the affinity of EF-Tu-kirromycin-GTP for aminoacyl-tRNA, just like it does in the absence of the antibiotic.

Biochemistry, 1991 Jul 9, 30(27), 6711 - 5
Selective DNA cleavage by elsamicin A and switch function of its amino sugar group; Uesugi M et al.; We report guanine-specific recognition and selective cleavage of DNA by the antitumor antibiotic elsamicin A equipped with an amino sugar and compare these results with cleavage by chartarin and chartreusin antibiotics . The preferential cutting sites of DNA strand scission with elsamicin A are on the bases adjacent to the 3'-side of guanine residues such as 5'-GN sites, in particular 5'-GG sites . The present results also indicate that (1) the aglycon portion binds intercalatively to the 3'-side of guanine in host DNA, (2) the guanine 2-amino group has an important effect on selective DNA binding of elsamicin A, and (3) the amino sugar residue of elsamicin A facilitates the drug binding into the minor groove of B-DNA . In addition, we found that an acetylation of the amino group on the elsamicin A sugar portion plays an interesting switch function for the activity of elsamicin A . The biological implication of this switch has also been discussed.

FEBS Lett, 1991 Jul 8, 285(1), 145 - 8
A novel protein phosphatase inhibitor, tautomycin . Effect on smooth muscle; Hori M et al.; The antibiotic, tautomycin, was found to be a potent inhibitor of protein phosphatases and equally effective for the type-1 and type-2A enzymes . For the catalytic subunits of the type-1 and type-2A phosphatases the IC50 value was 22 to 32 nM . For the phosphatase activity present in chicken gizzard actomyosin the IC50 value was 6 nM . Tautomycin had no effect on myosin light chain kinase activity . Tautomycin induced a Ca(2+)-independent contraction of intact and permeabilized smooth muscle fibers and this was accompanied by an increase in the level of myosin phosphorylation . Thus, tautomycin by virtue of its ability to inhibit phosphatase activity is a valuable addition for studying the role of protein phosphorylation.

Brain Res, 1991 Jul 5, 553(1), 135 - 48
Fluoro-Gold: composition, and mechanism of uptake; Wessendorf MW; Determining the mechanism by which fluorescent retrograde neuronal tracers are taken up requires knowledge of their composition . It has been claimed that Fluoro-Gold, a retrogradely transported fluorescent neuronal tracer, is 2-hydroxy-4,4'-diamidinostilbene (hydroxystilbamidine), an amidine antibiotic . However, this appears questionable, since the fluorescence spectrograms reported for Fluoro-Gold differ markedly from the spectrograms previously reported for purified hydroxystilbamidine . To help clarify the mechanism by which Fluoro-Gold might be taken up, it was decided to examine its composition and determine whether hydroxystilbamidine was its active agent . Fluoro-Gold was found by mass spectrometry to contain a component with a molecular weight of 280 Da (identical to that of hydroxystilbamidine), and fluorescence spectroscopy demonstrated the existence of a substance with a fluorescence spectrum similar to that of purified hydroxystilbamidine . Although a major fluorescent impurity was also observed, chromatographic separation of different fluorescent components of Fluoro-Gold suggested that the fraction resembling hydroxystilbamidine was responsible for its retrograde labeling of cells . It is concluded that hydroxystilbamidine is the active constituent of Fluoro-Gold . Chemically, hydroxystilbamidine is a weak base . In this respect it resembles True blue, DAPI, Granular blue, bis-benzimide, Nuclear yellow, and several other retrogradely transported molecules . It is suggested that these agents cross cell membranes in their uncharged form and are trapped in lysosomes and endosomes by a favorable pH gradient . Thus, the uptake of this type of retrograde tracer may be an example of a well-understood process occurring widely throughout biological systems: the trapping of weak bases in acidic cellular compartments.

Biochem Pharmacol, 1991 Jul 5, 42(2), 431 - 7
Inhibition of cellular thymidylate synthesis by cytotoxic propenal derivatives of pyrimidine bases and deoxynucleosides; Kalman TI et al.; A series of cytotoxic propenal (3-oxoprop-1-enyl) derivatives of pyrimidine bases and deoxynucleosides was evaluated for their ability to block thymidylate synthesis in intact and permeabilized murine leukemia L1210 cells . Several were potent inhibitors of this process, likely contributing to their cytotoxicity . The IC50 values of thymidine-3-propenal, the prototype of this series, in intact and permeabilized L1210, L-M and L-M(TK-) cells were 21, 7.5, and 75 microM and 1.5, 1.7, and 3.5 microM, respectively . The related base analogue, thymine-1-propenal, is a product of bleomycin-induced DNA strand-scission; the results of the present study bear on the mode of action of this antibiotic.

Med Clin North Am, 1991 Jul, 75(4), 815 - 29
Helicobacter pylori: aggressor or innocent bystander?
Clearfield HR.
Helicobacter pylori seeks gastric mucosa, whether found in the stomach, duodenum, or Barrett's esophagus . Definitive diagnosis can be secured by appropriate stains of mucosal biopsies and culture, but the rapid urease test, breath isotope studies, and serologic testing are also useful . The frequency of colonization increases with advancing age, but infection occurs earlier in underdeveloped countries . Although the reservoir is uncertain, water or food transmission seems likely . There is sufficient evidence to assign an etiologic role to the bacteria in the causation of type B antral gastritis . H . pylori is found in areas of gastric metaplasia within the duodenum and is associated with duodenitis . Although acute infection leads to hypochlorhydria, chronic colonization has little effect on acid secretion . Studies have thus far failed to establish a convincing relationship between H . pylori and nonulcer dyspepsia, although the bacteria may play a role in selected patients . H . pylori is found in association with most idiopathic gastric and duodenal ulcers, but it is unclear as to whether the bacteria plays a causative or permissive role . The organism has a predilection for intercellular spaces and the mucous layer, thus affording relative isolation from luminally active antibiotics . Monotherapy with bismuth preparations transiently eliminates the bacteria, but recolonization is rapid, probably due to regrowth of sequestered organisms . A combination of metronidazole, bismuth, and tetracycline (or amoxicillin) affords the best eradication rate, but the potential side effects of this program should be considered . The present therapy of duodenal ulcer disease is effective and without significant risk . Treatment of H . pylori should be reserved for those patients who relapse on adequate maintenance therapy . If a safe and effective antibiotic becomes available, more frequent testing and earlier treatment intervention may become more attractive . H . pylori is probably an "innocent bystander" for most patients, but the bacteria may sufficiently impair the defenses of the antral and duodenal mucosa to facilitate the development and relapse of ulcer disease in subsets of patients.

Mutat Res, 1991 Jul, 263(3), 165 - 71
Transfection of wild-type and 'Fanconi anemia-like' mouse lymphoma mutant cells by electroporation; Fraser D et al.; An electroporation protocol for the successful transfection of mouse lymphoblastoid cells has been developed . Two cell lines, a normal and a mutant sensitive to DNA cross-linking agents, were used . The optimum conditions of electroporation in terms of uptake of the fluorescent dye lucifer yellow coupled with low toxicity were established . Subsequently, these conditions were used to achieve stable transfection by a plasmid expression vector . The plasmid integration patterns were determined by Southern blot analysis.

Medicine (Baltimore), 1991 Jul, 70(4), 246 - 56
Secondary systemic amyloidosis: response and survival in 64 patients; Gertz MA et al.; From 1956 through 1989, 38 men and 26 women were seen at the Mayo Clinic with biopsy-proven AA . The underlying disorder was rheumatic disease in 42, infectious disease in 11, inflammatory bowel disease in 6, and other causes in 5 . All patients were symptomatic at the time of diagnosis . Fifty-eight of the 64 patients had proteinuria or renal insufficiency . Fourteen also had significant symptoms of gastrointestinal amyloid, and 6 had amyloid goiter . None of the patients had symptomatic cardiac involvement, and only 3 had palpable hepatomegaly . Renal, gastric, rectal, fat, and marrow biopsies were positive for amyloid in 100%, 94%, 82%, 58%, and 46% of tested patients, respectively . The median survival of the entire group was 24.5 months . Thirty-five of the 47 deceased patients died as a direct result of their amyloidosis, primarily from complications of renal failure . Nine were successfully treated and had regression of the disease . Two with bronchiectasis responded to long-term cyclic antibiotic therapy, as did 1 patient with osteomyelitis . One patient with inflammatory bowel disease responded to surgical resection, and 1 with familial Mediterranean fever responded to colchicine . Four patients with rheumatic disease were treated with cyclophosphamide (in 2) and methotrexate (in 2), with complete resolution of their renal disease . All 9 successfully treated patients are alive, with a median follow-up of 58 months . Statistical analysis revealed that creatinine values greater than or equal to 2.0 mg/dl (P less than 0.003) and a serum albumin value less than 2.5 g/dl (P less than 0.02) were associated with a poorer survival . The single strongest variable associated with poor survival was a serum creatinine level greater than 2 mg/dl at presentation, with a median survival of 11.2 months compared to patients with a creatinine level less than 2.0 mg/dl, with a median survival of 56.9 months.

Laryngoscope, 1991 Jul, 101(7 Pt 1), 709 - 16
Toxic effects of cisplatin alone and in combination with gentamicin in stria vascularis of guinea pigs; Kohn S et al.; The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs . The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem-evoked response audiometry . The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low-dose cisplatin alone or in combination with gentamicin . Bilateral deafness resulted from high-dose cisplatin combined with gentamicin . The combined treatment produced prominent structural damage in the stria vascularis . The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin.

Chest, 1991 Jul, 100(1), 14 - 6
Acute asthma . Admission chest radiography in hospitalized adult patients; White CS et al.; The utility of admission chest radiography has been controversial in the management of adult patients admitted to the hospital with acute asthma . We reviewed the impact of admission chest radiography on in-hospital management of 54 adult patients with acute asthma . Each patient was admitted after a failed 12-h course of bronchodilator therapy in the emergency ward . Major radiographic abnormalities were found in 20 (34 percent) of 58 occasions . These abnormalities included focal parenchymal opacities, IIM, enlarged cardiac silhouette, pulmonary vascular congestion, new solitary pulmonary nodule and pneumothorax . Subsequent antibiotic use correlated with radiographic focal opacities or IIM, even in afebrile patients, but did not correlate with elevated blood leukocyte count . Based on the evidence of in-hospital alteration of management independent of elevated blood leukocyte count and body temperature, we recommend that chest radiographs be obtained for all adult patients admitted because of acute asthma.

Am Surg, 1991 Jul, 57(7), 409 - 13
Nonoperative management of splenic injuries; Oller B et al.; The traditional management of splenic trauma has undergone major revision in recent years . Given the physiological importance of the spleen, certain controversy has arisen regarding the most appropriate method of managing this type of trauma . Nonoperative therapy in children has proven to be successful not only in the case of kidney lesions but also for splenic lesions . Nonoperative management carried out in the authors' hospital on a group of 56 patients (49 adults and seven children over the age of 7 years) has proved successful in 37 cases . The success of this technique requires a well-formulated protocol, diagnostic methods (ultrasound and computed tomography), rigorous patient control in the emergency room during the initial phase (first 48 hours), the availability of a medical team if surgical intervention becomes necessary (persistent or recurrent hemorrhage), and complementary measures which facilitate the cicatrization of the splenic injury (bed rest, antibiotic therapy).

Am J Public Health, 1991 Jul, 81(7), 923 - 5
The use of direct mail to increase clinician knowledge: an intervention study; Sadowsky D et al.; A probability sample of American general practitioner dentists, 40 years of age or older, in solo private practice, was the target of two direct mail interventions offered at two different times, to test whether knowledge regarding prophylaxis of patients at risk for infective endocarditis could be improved . Tests of knowledge were responses in a mail questionnaire to clinical vignettes, designed to elicit the content of antibiotic regimens used for patients at risk . The research design enabled detection of (1) the effect of the interventions; (2) the differences in their effect; (3) the attenuation of their effect; and (4) the effect of time . Where baseline knowledge was low, it was improved and did not rapidly disappear . Both mail interventions were equally effective, in most instances, and there was no attenuation of the interventions' effect and no effect of time on the control groups' knowledge over a 4 1/2 month period . The results suggest that it is possible to improve clinicians' knowledge of expert recommendations through direct mail intervention.

Radiology, 1991 Jul, 180(1), 61 - 4
Pseudomembranous colitis: sonographic features; Downey DB et al.; The sonographic features of pseudomembranous colitis (PMC) are described in 13 patients and correlated with clinical, radiologic, and pathologic findings . At sonography, the wall of the entire colon was moderately to markedly thickened in all patients . The enlarged colon wall was most commonly shown as a wide band of heterogeneous medium echogenicity surrounded by a narrow hypoechoic layer . Pathologic correlations proved that the wide inner stratum represented severely edematous submucosa and mucosa, while the outer layer depicted the muscularis propria . Almost complete effacement of the lumen of the colon occurred secondary to the mural edema in 69% of the cases . The dearth of intraluminal gas combined with thickening of the colon wall and ascites facilitated excellent sonographic evaluation . The diagnosis of PMC is strongly suggested by the presence of these sonographic features in a patient with watery diarrhea and a history of antibiotic therapy.

Radiology, 1991 Jul, 180(1), 57 - 60
Pseudomembranous colitis: CT evaluation of 26 cases; Fishman EK et al.; Pseudomembranous colitis (PMC) is an infectious colitis usually occurring as a complication of antibiotic use . The computed tomographic (CT) appearances of 26 patients with PMC were reviewed . Twenty-three patients demonstrated an abnormal bowel wall, with an average wall thickness of 14.7 mm (range, 3-32 mm); in three patients, bowel wall thickness was normal . Contrast material trapped between thickened folds corresponded to the broad transverse bands described on plain radiographs . Pancolonic involvement was seen in 13 cases, while seven patients had right-sided involvement only; three patients had bowel wall thickening limited to the rectosigmoid only . Although the CT appearance of PMC is not highly specific, the diagnosis may be suggested in the proper clinical setting.

Plast Reconstr Surg, 1991 Jul, 88(1), 111 - 4
Management of early human bites of the hand: a prospective randomized study; Zubowicz VN et al.; A prospective, randomized study was undertaken to determine if mechanical care of early human bites alone is sufficient therapy in the compliant patient or if prophylactic antibiotics (oral versus parenteral) are indicated . Beginning in June of 1985, patients presenting with human bites of the hand were entered into the study if (1) the bite was less than 24 hours old, (2) the patient was free of infection, (3) the bite did not penetrate the joint capsule, and (4) there was no injury to tendon . Forty-eight patients were ultimately segregated into one of three study groups after standardized ER mechanical wound care . Fifteen patients received an oral placebo, with 7 developing infection (46.7 percent) . Sixteen patients received an oral antibiotic, and 17 patients received parenteral antibiotics . No infections were found in either of these latter groups . The results statistically substantiate that mechanical wound care alone is insufficient therapy . Oral antibiotics appear to be equal to intravenous antibiotics for prophylaxis . From a cost-benefit standpoint, vigorous cleaning, debridement, and coverage with a broad-spectrum oral antibiotic are adequate care for an uncomplicated bite in the compliant patient.

Obstet Gynecol, 1991 Jul, 78(1), 50 - 5
Diagnostic imaging in puerperal febrile morbidity; Lev-Toaff AS et al.; This retrospective study was conducted to assess the value of imaging in patients with refractory puerperal febrile morbidity . During a 36-month period, 31 patients were referred for ultrasound and/or computed tomography or magnetic resonance imaging because of postpartum fever unresponsive to broad-spectrum antibiotic therapy of at least 72 hours' duration . Hematomas were identified in 11 women . Abscesses were diagnosed in seven patients, ovarian venous thrombosis in two, vesicouterine fistula in one, small-bowel obstruction in one, and a subcutaneous seroma in one . Twenty-one women had endomyometritis, 13 of whom also had other extrauterine abnormalities (abscess in six, hematoma in four, and ovarian venous thrombosis, vesicouterine fistula, and small-bowel obstruction in one each) . Retained placental tissue was found in two women with endomyometritis . Only two subjects had negative imaging studies . In most patients, imaging led to definitive diagnosis and specific therapeutic measures resulting in resolution of the febrile morbidity . Our experience suggests that these imaging techniques may be helpful in evaluating puerperal fever.

Antibiot Khimioter, 1991 Jul, 36(7), 29 - 32
{Effect of hemosorption on the elimination of an amphotericin B derivative in experimental studies}; Vetkina IF et al.; Possible extracorporeal removal of a novel water soluble derivative of amphotericin B (NWSDA) from the host was studied . The bench tests demonstrated that actilen, a fibrous carbon adsorbent, was the optimal carbon sorbent for sorption of NWSDA . It was shown in the acute experiments on animals that during the hemosorption the antibiotic blood concentration on the outlet of the column was significantly lower than that on the inlet . Still, the NWSDA concentration in the blood lowered slowly which was likely due to the return of the antibiotic to the blood from the tissues.

Anesteziol Reanimatol, 1991 Jul-Aug, (4), 28 - 32
{Lymphogenic methods of treatment in multiprofile intensive care units}; Stashchuk VF; The advantages of lymphogenic techniques (closed antibiotic perfusion into the lymphatic system) have been shown in 203 surgical patients, as compared to 210 control patients to whom an antibiotic was administered by the current technique . The clinical and economic effect obtained was manifested in a shorter hospital stay, decreased lethality, reduced drug consumption per course of treatment, etc . In 92 cases of severe endo- and exotoxemias of various etiology, accompanied by hepatic or hepatorenal failure the possibility of open perfusion of the lymphatic system which incorporated lymphosorption with CKH type sorbent followed by lymph sanitation with kanamycin (50 mg/kg) before its reinfusion has been shown.

Zentralbl Veterinarmed A, 1991 Jul, 38(6), 418 - 26
Experimental induction of diarrhoea in newly-weaned piglets; Cox E et al.; To induce diarrhoea and hypovolaemia, newly-weaned conventionally bred piglets (3- to 4-weeks-old), were either given secretagogues or were inoculated with enterotoxigenic Escherichia coli (ETEC) . Choleratoxin (n = 2), E . coli heat-labile enterotoxin (n = 2) or castor oil (n = 2) were given intragastrically or piglets were intraperitoneally injected with DL 5-hydroxytryptophan (n = 3) . These substances induced a transient diarrhoea without clinical symptoms of dehydration . Therefore, a combination of castor oil and DL 5-hydroxytryptophan was given two times a day during 3 consecutive days to 3 piglets . Although diarrhoea lasted for 5 days, still no hypovolaemia occurred . Probably the secretagogues have to be given continuously to mimic the continuous release of enterotoxins during secretory colibacillary diarrhoea . It was, therefore, tried to reproduce colibacillosis in the just-weaned piglets . Animals were inoculated with K88ac fimbriae producing ETEC strains (O149:K91:K88ac; LT, STa and STb positive) (n = 7), or pretreated with chloramphenicol followed by the ETEC inoculation (n = 8), or pretreated with the antibiotic, inoculated with an enteropathogenic coronavirus, transmissible gastroenteritis virus (TGEV), and subsequently inoculated with ETEC (n = 18) . Only the last procedure induced a reproducible diarrhoea (93%) and dehydration resulting in a mortality of 80% . It was concluded that the latter experimental procedure could be used to study diarrhoea and hypovolaemia in newly-weaned piglets and to evaluate the effect of potentially antisecretory drugs on postweaning diarrhoea in piglets.

J Microencapsul, 1991 Jul-Sep, 8(3), 381 - 9
Encapsulation of drugs into large unilamellar liposomes prepared by an extemporaneous method; Liautard J et al.; The method we developed for extemporaneous preparation of large unilamellar liposomes (Philippot et al . 1984) was applied to the encapsulation of 12 different antibiotic, anti-asthmatic and anti-inflammatory drugs . The behaviour of these drugs, during encapsulation, assigns them to one of the three classes: hydrophilic, hydrophobic or both . Alone, the first type of compound gave an appreciable encapsulation . However, the entrapment yield depended on the respective charges of the liposome and the drug . The amphiphile molecules tested are permeant and thus did not stay inside the liposomes . Only one of the hydrophobic drugs analysed associated with the liposome membrane lipids with a good yield.

J Am Osteopath Assoc, 1991 Jul, 91(7), 677 - 86
Pentoxifylline as adjunctive therapy in leg ulcer management; Brenman SA; Refractory or recurring leg ulcers typically signify the presence of impaired venous or arterial microcirculation (or both) . A current hypothesis suggests that local oxygen and nutrient deficits occur because capillary lumens narrow and become permeable to fibrinogen and proteins by activated white blood cells and inadequate fibrinolysis . As a result, the deposition of a relatively impermeable perivascular fibrin sheath occurs, preventing adequate delivery of oxygen and nutrients . Therapy should therefore aim at reversing these deficits and improving wound healing . Pentoxifylline (Trental), used in combination with local wound care and appropriate antibiotic therapy, has been successful in significantly improving the healing of refractory leg ulcers . Pentoxifylline can reverse the abnormal function of white and red blood cells and platelets, as well as reduce blood viscosity and vascular permeability . The mechanisms of action of pentoxifylline are described in light of current hypotheses pertaining to leg ulcer development . Also discussed are nine cases in which pentoxifylline, when added to previously unsuccessful local wound care, either improved or healed the refractory ulcers.

Monatsschr Kinderheilkd, 1991 Jul, 139(7), 418 - 20
{LFA-1 defect: a rare granulocyte function disorders as a cause of therapy-resistant omphalitis in newborn infants}; Hoek T et al.; A newborn infant suffered from severe omphalitis resistant to antibiotic therapy . The combination of the symptoms: delayed separation of the umbilical cord, omphalitis, impairment of wound-healing and extreme leukocytosis led to the diagnosis of LFA-1 (leukocyte function antigen)-deficiency, which was confirmed by monoclonal antibodies . The pathophysiology of this disorder is described shortly.

Khirurgiia (Mosk), 1991 Jul, (7), 28 - 32
{Immunomodulating therapy of a suppurative infection of the soft tissues}; Bobrova NV et al.; The initial immunological status in patients with purulent infection of the soft tissues is characterized by T-cell deficiency and relative hyperfunction of the B-immunity . The risk group with Grade 2-3T-cell immune deficiency takes up 44.5-77.5% and is encountered in patients with the B blood group and positive Rh factor in 79.1 +/- 5.2 and 70.8 +/- 4.3% of cases, respectively . Combination of sodium nucleinate and autohemotransfusion with the traditional therapy raises its efficacy . This is attended by correction of immunological disorders in T-cells and phagocytes, facilitates cleansing of the foci and increase of antibiotic sensitivity of the flora, and shortens the term of treatment.

Khirurgiia (Mosk), 1991 Jul, (7), 108 - 13
{Means of preventing suppurative complications following surgery of the liver}; Vishnevskii VA et al.; The article analyses the results of antibiotic prevention of postoperative infectious complications and the use of special techniques and operative manipulations in 60 patients with localized affections of the liver . It was found that the most effective method of antibiotic prevention of complications is a purposeful transport of antibiotics in autologous erythrocytic shadows, which are infused intravenously once before the operation and, in extensive resection of the liver, on the second or third postoperative day . With the use of special techniques and operative manipulations in combination with purposeful transport of antibiotics the frequency of infectious complications reduces and the results of treatment in surgery of localized affections of the liver improve.

Nippon Jibiinkoka Gakkai Kaiho, 1991 Jul, 94(7), 980 - 9
{Retropharyngeal hematoma following a bruise of head and neck--a case report and review of literature}; Haraguchi K et al.; Diseases affecting the retropharyngeal space are relatively uncommon, much less a case of retropharyngeal hematoma . However, a space-occupying lesion in this area can be life threatening and require emergency surgical intervention . There have been 46 cases of retropharyngeal hematoma reported in the English literatures from 1934 to 1989, but there has been no reported case in Japan . Recently we treated a 72-year-old male sustained retropharyngeal hematoma following a bruise of head and neck . The patients was received tracheostomy, antibiotic therapy and intravenous hyperalimentation, and this hematoma was resolved in about 2 weeks . The etiologies, diagnosis, therapies in our case and prognoses of the literature reviewed 47 cases of retropharyngeal hematoma were discussed comprehensively.

J Heart Lung Transplant, 1991 Jul-Aug, 10(4), 614 - 6; discussion 616-7
Recycled heart valves from transplant patients; Feindel CM et al.; Forty heart transplantations were performed at the Toronto Western Hospital, University of Toronto, from October 1987 to December 1989 . Each heart extracted from a recipient was examined with the view of using the aortic valve as a homograft for another patient requiring aortic valve replacement . Of the 40 explanted hearts, 26 had normal aortic valves that were potentially suitable for homografting, and 14 had aortic valves judged as unsuitable . Of the potentially suitable valves, four were preserved for ex vivo arrhythmia studies requiring aortic root perfusion and four were damaged during harvesting . The remaining 18 usable valves were sized at the time of explantation and stored in an antibiotic solution at 4 degrees C . Thirteen valves were transplanted within 10 days of harvesting, and five were discarded because no suitable recipients were available within this period . There were no operative deaths or valve-related complications in the 13 homograft valve recipients . Mean follow-up was 13 months (range, 3 to 27 months) . One patient required replacement of the homograft with a mechanical prosthesis because of insufficiency and stenosis . All patients are alive, are New York Heart Association functional class status I, and have insignificant valve gradients based on Doppler echocardiography . Although hearts removed from transplant recipients are severely diseased, the aortic valves are frequently normal and should be considered for use as homografts for other patients requiring aortic valve replacement.

J Bacteriol, 1991 Jul, 173(14), 4482 - 92
Stationary-phase-inducible "gearbox" promoters: differential effects of katF mutations and role of sigma 70; Bohannon DE et al.; Many of the changes in gene expression observed when Escherichia coli cells enter stationary phase are regulated at the level of transcription initiation . A group of stationary-phase-inducible promoters, known as "gearbox" promoter, display a characteristic sequence in the -10 region which differs greatly from the consensus sequence for sigma 70-dependent promoters . Here we describe our studies on the gearbox promoters bolAp1 and mcbAp, responsible for the temporally regulated transcription of bolA and the genes involved in the synthesis of the peptide antibiotic microcin B17, respectively . Deletion analysis of mcbAp demonstrated that the stationary-phase-inducible properties of this promoter are found in a DNA fragment extending from -54 to +11 bp, surrounding the transcriptional start site, and are separable from DNA sequences responsible for the OmpR-dependent stimulation of transcription of mcbAp . In vitro transcription studies indicate that the RNA polymerase holoenzyme involved in the transcription of mcbAp contains sigma 70 . In this and an accompanying paper (R . Lange and R . Hengge-Aronis, J . Bacteriol . 173: 4474-4481, 1991), experiments are described which show that the product of katF, a global regulator of stationary-phase gene expression and a putative sigma factor, is required for the expression of bolAp1 fused to the reporter gene lacZ . In contrast, mcbAp appears to be negatively regulated by katF . We discuss the implications of these results for postexponential gene expression and the role of gearbox sequences in the regulation of promoter activity.

Nippon Kyobu Geka Gakkai Zasshi, 1991 Jul, 39(7), 1005 - 10
{Therapeutic guide line for hemoptysis}; Masuda H et al.; We report the result of treatment for thirty-two patients whose chief complaint was hemoptysis and represent the therapeutic guide line for hemoptysis . In thirty-two cases, there were twenty men and twelve women and average of age was fifty-two years old . Twenty-nine of them were chronic lung diseases such as tuberculosis and bronchiectasis and only three cases have malignant tumors . Two of them recovered with conservative therapy and bronchial arteriography (BAG) have been performed in thirty patients in order to determine the bleeding foci, BAG was failed in two cases, but these two cases have been recovered with following up, BAG was succeeded in twenty-eight cases and twelve cases of them could not been determined the bleeding foci by angiography and could be controlled using hemostatic and antibiotic agents . Embolization of bronchial arteries with gelatin sponge have been performed in sixteen cases and made success in eleven cases . In ten of these cases, BAE was effective less than two times . Only one of silicosis with restrictive lung function was considered contraindication of surgery and recovered by three times of BAE . Four cases of five uneffective BAE (rebleeding after two times of BAE) have been treated by operation in good course . But one case complicated with WPW syndrome has died because of aspiration pneumonia without operation . In our institute, the rate of operation for hemoptysis was low as 13% of thirty-two cases . In order to consider the indication of surgery, bronchial arteriography was essential to determine bleeding foci and BAE was effective in over 80% of hemoptysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Plast Surg, 1991 Jul, 18(3), 515 - 23
Update on chronic osteomyelitis; Anthony JP et al.; Recent advances in the understanding of the pathophysiology and treatment of osteomyelitis have been discussed . Some of the advances (in either knowledge or technology) that we have found particularly useful include the following: The discovery of additional prognostic factors, which allow more reliable preoperative assessment . The development of the Ilizarov device, which allows bone fixation and later limb lengthening . Confirmation of the effectiveness of single-staged debridement and muscle flap closure . Confirmation that a brief (10 to 14 day) course of antibiotics is as effective as more prolonged therapy . The development of several new free muscle donor sites and a greater appreciation of the need for careful insetting of the muscle . The development of local antibiotic delivery systems, especially continuous antibiotic irrigation catheters . The development of newer oral and intravenous antibiotics that allow outpatient therapy following surgery . The recognition that patients require extended follow-up, and that any recurrences can be successfully treated with a second debridement and muscle flap closure.

Kyobu Geka, 1991 Jul, 44(7), 573 - 5
{Tricuspid endocarditis related to a residual ventricular septal defect: a case report of successful tricuspid valvuloplasty}; Yamanaka K et al.; A 5-year-old girl presented infected tricuspid valve related to a residual ventricular septal defect . Antibiotic therapy produced a satisfactory initial improvement . However, subsequent deterioration with uncontrolled infection, in spite of alterations of the antibiotic regime, necessitated surgical intervention . Because the lesion was localized to the anterior leaflet of the tricuspid valve, partial excision of this leaflet and patch was undergone with a sustained clinical improvement with minimum residual valvular incompetence . This experience supports the concept that tricuspid valvuloplasty is the method of choice in the treatment of patient with regional right-sided infective endocarditis.

J Antibiot (Tokyo), 1991 Jul, 44(7), 785 - 92
Inactivation of fusidic acid by resistant Streptomyces strains; von der Haar B et al.; Streptomyces lividans and several other Streptomyces species are resistant to the steroid-like antibiotic fusidic acid . This resistance is mediated by structural modification of the antibiotic . Using TLC, CD, UV, IR, NMR and mass spectroscopy the structure of one of the resulting inactive compounds was determined . It is derived from fusidic acid by the loss of an acetyl group and the formation of a lactone ring between C-21 and C-16 . In addition, helvolic acid, a compound closely related to fusidic acid, has been shown to be modified.

J Antibiot (Tokyo), 1991 Jul, 44(7), 774 - 84
Synthesis and nematocidal activities of jietacin A and its analogs; Tsuzuki K et al.; Simple, efficient syntheses of jietacin A, a nematocidal antibiotic, and its analogs have been developed in order to study structure-activity relationships . A series of alpha,beta-unsaturated azoxy compounds was prepared from phenylselenomethyl azoxy compounds as key intermediates and its nematocidal activity was determined.

Br J Surg, 1991 Jul, 78(7), 838 - 40
Necrotizing fasciitis; Asfar SK et al.; Ten cases of necrotizing fasciitis are reviewed . Three patients died but only two of these deaths were due to uncontrolled septicaemia . All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice . Prompt and aggressive surgical debridement remains the cornerstone of management.

Surgery, 1991 Jul, 110(1), 99 - 103
The surgical management of superficial infections caused by atypical mycobacteria; Plaus WJ et al.; We have recently treated four patients with atypical mycobacterial skin infections . Two patients were infected with Mycobacterium smegmatis after self-injection with a veterinary-grade anabolic steroid . To our knowledge, this complication has not been previously described . The other patients had steroid-dependent asthma and lower extremity infections involving M . kansasii and M . chelonei after minor household trauma developed . Atypical mycobacterial skin infections may be seen as chronic ulcerations with violaceous edges, rolled margins, and significant subcutaneous necrosis . An indolent course and the clinical appearance may aid in diagnosis . In our experience, limited incision and drainage or dressing changes fail to eradicate these infections, even when accompanied by appropriate antibiotic therapy . Successful treatment requires aggressive debridement of all infected subcutaneous tissues and skin . Split-thickness skin grafting was successfully used to cover large wounds . Grafting did not appear to foster recurrent infection.

Surg Gynecol Obstet, 1991 Jul, 173(1), 49 - 53
Transduodenal exploration of the common bile duct in patients with nondilated ducts; Ratych RE et al.; Exploration of the small common bile duct can be technically difficult and is associated with a significant risk of ductal injury or late stricture, or both . Transduodenal common duct exploration after sphincteroplasty (TCDE/S) is an alternative method of duct exploration that avoids choledochotomy . Cholecystectomy followed by TCDE/S was performed upon 28 patients with nondilated ducts and suspected choledocholithiasis . Common duct stones were retrieved in 17 patients . Failure to retrieve stones in the remaining 11 patients was attributed to either false-positive results of cholangiography, forceful passage of stones into the duodenum during the initial insertion of a Fogarty catheter through the cystic duct or a false-negative finding at duct exploration . There was no perioperative mortality . Two patients had asymptomatic postoperative hyperamylasemia . One patient had postoperative pancreatitis, hyperbilirubinemia and cholangitis that resolved with antibiotic therapy by the eighth postoperative day . Other complications included wound infection, delayed gastric emptying, pneumonia and otitis media . The over-all morbidity rate was 28.6 per cent . Long term follow-up was obtained in all 28 patients . All patients in the follow-up group are free of recurrent biliary tract disease . TCDE/S appears to be a safe and effective method of exploring the nondilated common bile duct.

J Thorac Imaging, 1991 Jul, 6(3), 80 - 8
Surgical management of thoracic empyema; Wallenhaupt SL; Thoracic empyema usually results from pulmonary infection or thoracic surgery . Antibiotic therapy is an essential part of the treatment, but surgical techniques to drain the pleural fluid and obliterate the empyema space often are required . A wide range of closed and open surgical techniques are available . This article reviews the various surgical options for the treatment of nontuberculous bacterial empyema secondary to pulmonary infection in the patient with a normal immune response . Emphasis is placed on a thorough understanding of the pathophysiology and natural history of empyema for selection and timing of appropriate treatment . Thoracic imaging techniques play a substantial role in the evaluation and treatment of empyema and in assessing the outcome of surgical therapy.

Am J Hematol, 1991 Jul, 37(3), 197 - 200
Warfarin skin necrosis: recurrence in the absence of anticoagulant therapy; Humphries JE et al.; Skin necrosis is a well-known yet rare complication of oral anticoagulant therapy . We report the unusual recurrence of lesions typical of warfarin skin necrosis in the absence of anticoagulant therapy . A 59-year-old woman developed skin necrosis while receiving prophylactic warfarin following the detection of a large left ventricular thrombus . The warfarin was discontinued and the lesions improved . One month later new areas of skin necrosis developed although the patient had received no further warfarin . Progressive congestive heart failure, poor nutrition, and prolonged oral antibiotic therapy preceded the recurrence . Vitamin K deficiency was present on admission . The potential role of vitamin K-dependent coagulation factors in the pathogenesis of anticoagulant-associated skin necrosis is discussed.

Orthop Clin North Am, 1991 Jul, 22(3), 531 - 8
Management of total knee arthroplasty infection; Windsor RE; The treatment of infected total knee arthroplasty represents the most difficult form of revision surgery . Successful salvage of this complication can be accomplished only by extensive investment of surgical and infectious disease efforts in eradicating the infection . A two-stage reimplantation procedure for treating this condition has been the most successful functional option and should be utilized whenever possible to definitively eradicate the infection and ensure good function of the knee joint . It is the procedure of choice for younger healthy patients who can medically tolerate the protocol . Other options may be necessary as the medical condition of the patient dictates . Initial debridement with antibiotic suppression and antibiotic suppression alone have yielded limited successful results but can be accomplished only in a small number (23%) of patients.

Behring Inst Mitt, 1991 Jul, (89), 198 - 208
Manipulation of the biosynthesis of protein-modifying glycoconjugates by the use of specific inhibitors; Schwarz RT; Since it is possible to interfere with different steps in the dolichol pathway of protein glycosylation and in the processing of N-linked oligosaccharides information can be deduced as to the role of protein-bound carbohydrate by comparing the biochemical fates and functions of glycosylated proteins with their non-glycosylated counterparts, or with proteins exhibiting differences in the type of oligosaccharide side-chains . Cells infected with enveloped viruses are excellent model systems for studying the inhibition of protein glycosylation, since they contain a restricted number of glycoproteins, in some cases with well-defined functions . Tunicamycin, an antibiotic, as well as several sugar analogues have been found to inhibit the glycosylation of proteins by virtue of their antiviral properties . They interfere with different steps in the dolichol pathway of N-glycosylation resulting in a lack of functional lipid-linked oligosaccharide precursors . Trimming inhibitors, a second generation of inhibitors of glycosylation, interfere with the processing of oligosaccharides by specific glucosidases and mannosidases, resulting in a block of the conversion of high-mannose to complex-type oligosaccharides . Depending upon the compound used, glycoproteins contain glucosylated-high-mannose, high-mannose, or hybrid oligosaccharide structures instead of complex ones . Various effects of glycosylation inhibitors have been described: susceptibility to proteases, improper protein processing and misfolding of polypeptide chains, loss of biological activity, and alteration of the site of virus-budding . A third generation of inhibitors of glycosylation is emerging which are designed to interfere with late steps of N-glycosylation occurring after trimming, to bring about changes in the makeup of complex carbohydrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Epilepsia, 1991 Jul-Aug, 32(4), 554 - 9
Allergic rash due to antiepileptic drugs: clinical features and management; Pelekanos J et al.; Optimal management of allergic rash from antiepileptic drugs (AEDs) is unclear . We identified 50 patients with 68 reactions (36 to one AED, 10 to two AEDs, and four to three AEDs) . The AEDs implicated were carbamazepine, 30; phenobarbital (PB), 20; phenytoin, 16; ethosuximide, one; and AED combination, one . Sixty-three reactions were cutaneous eruptions, three exfoliative dermatitis, and two Stevens-Johnson syndrome . Forty-six reactions were mild (rash only), 18 moderate (systemic symptoms or other organ system involvement), and four life-threatening (all with PB) . In most patients with greater than 1 reaction, the second and third reactions were not more severe than the first . Prior antibiotic allergies or nonmedication allergies were no more common than in a control group without reactions . The AED was ceased abruptly in 59 patients (22 of whom did not receive a new AED), tapered in five, and continued unchanged in four . Despite this, there was no status epilepticus (SE) during the reaction or its treatment, and no patient's seizure control deteriorated . In 40 cases, a new AED was added--16 after the reaction had resolved and 24 before total resolution . Rash recurred with the new AED in 50 and 42% respectively (NS) . We conclude that, though allergic rashes to AEDs are usually mild, the rare occurrence of severe reactions indicates that the AED should be ceased . This can be done abruptly with minimal risk of SE . A new AED can be added, if necessary, prior to the resolution of the rash without increasing the risk of further reactions.

Pept Res, 1991 Jul-Aug, 4(4), 239 - 44
The crystal structure of Z-Aib-Gly-Aib-Leu-Aib-OtBu, the synthetic, protected N-terminal pentapeptide of trichotoxin; Gessmann R et al.; Z-Aib-Gly-Aib-Leu-Aib-OtBu, the alpha-aminoisobutyric acid (Aib)-containing N-terminal pentapeptide of the antibiotic trichotoxin, has been studied by x-ray crystallography . The molecule forms a right-handed helix with a reversal of the sense of the helix at the C-terminus . Torsion angles and hydrogen bonding pattern are consistent with a mixed 3(10)-/alpha-helical conformation . In the crystal, continuous columns are formed by head-to-tail arrangement of hydrogen-bonded molecules along the helix axis . The helical columns associate via hydrogen bonds forming closely packed parallel pairs.

Zhonghua Wai Ke Za Zhi, 1991 Jul, 29(7), 408 - 11, 461
{Surgical intervention of infective endocarditis}; Xue GX; 33 patients with infective endocarditis were treated from 1980 to 1989 . 31 of them were operated on for primary endocarditis complicated by congenital heart disease (5 patients) and valvular heart disease (26 patients) . Two patients (6.5%) died postoperatively and 2 patients with primary endocarditis complicated by aortic insufficiency died without operation . In 10 patients with endocarditis secondary to open-heart surgery, 6 were reoperated upon but 5 of them died; in the remaining 4 who were not reoperated on died . We consider that surgical intervention for endocarditis, either primary or postoperative, should be taken as early as possible after a short period of ineffectiveness of antibiotic therapy.

Turk J Pediatr, 1991 Jul-Sep, 33(3), 163 - 6
IgG subclass deficiency in children with recurrent infections; Tezcan I et al.; IgG subclass levels were studied in 12 children, aged between 2.5-12 years with recurrent respiratory tract infections . They did not have low IgG levels or IgA deficiency . We found combined deficiency of IgG2-IgG4 in one patient and selective IgG2 deficiency in another (16.6% of patients) . These two patients had bronchiectasis due to recurrent severe pneumonia, however one patient with bronchiectasis had normal IgG subclass concentrations . Our IgG subclass-deficient patients who did not respond to prophylactic antibiotic therapy were given gammaglobulin therapy . IgG subclass deficiency should be considered in children with unexplained recurrent infections even in the presence of normal serum immunoglobulin levels.

Rinsho Shinkeigaku, 1991 Jul, 31(7), 734 - 7
{A case of spinal cord sarcoidosis with interesting MRI findings}; Yamashita M et al.; A case of spinal cord sarcoidosis was reported with special reference to MRI findings . A 15-year-old man was admitted to our hospital because of gait disturbance for last six months . Neurological examination on admission showed spastic paraparesis and posterior column signs . MRI of the cervical spinal cord revealed diffuse swelling and low intensity signal in T1-weighted sequences, diffuse high intensity signal in T2-weighted, and multiple micro-nodular lesion in Gd-DTPA enhanced T1-weighted . At first multiple sclerosis was suspected, although the data of cerebrospinal fluid was not suggestive . Four weeks after admission general fatigue, fever, cough, and headache appeared and the neurological symptoms got worse . Chest film and CT revealed diffuse small nodular shadows in the lung field . Abdominal ultrasonography and CT showed hepatosplenomegaly . The general condition became worse in spite of antibiotic and antituberculotic drug therapy, but remitted spontaneously in four weeks . MRI findings also exacerbated and improved during the same period, being compatible with neurological manifestations . The diagnosis of sarcoidosis was made by transbronchial lung biopsy which revealed sarcoid granuloma . Multiple small nodules on Gd-DTPA enhanced T1-weighted MRI had not been reported in patient with spinal cord sarcoidosis.

Z Naturforsch {C}, 1991 Jul-Aug, 46(7-8), 647 - 55
X-ray studies on phospholipid bilayers . XI . Interactions with chloramphenicol; Suwalsky M et al.; Chloramphenicol is a widely used antibiotic with low levels of toxicity . However, scanning electron microscopy revealed morphological changes in human erythrocytes when they interacted in vitro with therapeutical concentrations of chloramphenicol . To explain this shape change, a study concerned with the possible interactions of this antibiotic with bilayers built-up of phospholipids located in either side of the red cell membrane was performed by X-ray diffraction . Results indicated that chloramphenicol was unable to perturb in any significant extent the structure of the phospholipids under study . The only noticeable effects were phase transitions produced to dimyristoylphosphatidylethanolamine bilayers.

J Antimicrob Chemother, 1991 Jul, 28(1), 71 - 8
Isolation and identification of bacteria from subgingival plaque with low susceptibility to minocycline; Wilson M et al.; Twenty subgingival plaque samples from patients with chronic periodontitis were screened for the presence of three periodontal 'pathogens'--Porphyromonas gingivalis, Fusobacterium nucleatum and Eikenella corrodens . Nineteen of the samples were found to contain at least one of the three organisms and six samples contained all three . The subgingival plaque samples were cultured in the presence of various concentrations of minocycline, and those organisms which appeared to be least susceptible to the antibiotic were isolated and identified . A total of 40 isolates were obtained and these consisted of 18 different species, only one of which, Fusobacterium nucleatum, is generally recognized as being associated with chronic periodontitis . The minimum inhibitory concentrations of minocycline for many of the organisms isolated were greater than the concentration of attainable in gingival crevicular fluid following routine parenteral administration of the antibiotic.

J Intraven Nurs, 1991 Jul-Aug, 14(4), 261 - 7
Lower incidence of peripheral catheter complications by the use of elastomeric hydrogel catheters in home intravenous therapy patients; Strumpfer AL; A prospective study was conducted to compare the performance of a nonconventional short peripheral catheter made of elastomeric hydrogel material with that of the conventional short peripheral catheters used to administer intravenous therapy to patients before this study was undertaken . The catheters were inserted in home care patients, primarily diagnosed with Lyme disease, for the delivery of I.V . antibiotic therapy . The study results showed that the institutional 48-to-72-hour removal policy for conventional catheters is not practical for the elastomeric hydrogel test catheter . However, this policy indeed appears appropriate for conventional catheters because one half (50%) of the control catheters in this study and in other published studies failed within 72 hours compared with only 19% of the test catheters . This demonstrates that catheter material significantly affects catheter performance because the nonconventional catheters could be kept in place more than twice as long before causing the complication rates seen with the conventional control catheters at 3 days of dwell.

Anticancer Res, 1991 Jul-Aug, 11(4), 1373 - 8
A peptide from the GAP-binding domain of the ras-p21 protein and azatyrosine block ras-induced maturation of Xenopus oocytes; Chung DL et al.; The ras-oncogene-encoded p21 protein causes malignant transformation of NIH 3T3 cells and maturation of Xenopus oocytes when microinjected into these cells . P21 is known to interact with GTPase activating protein (GAP) intracellularly . Residues 32-45 of p21 have been implicated in interacting with GAP . In a previous study, we demonstrated that a synthetic peptide containing residues 35-47 from the GAP-binding region of p21 could block in vivo the effects of oncogenic p21 protein . It has also been found that an antibiotic, azatyrosine, blocks ras-initiated cell transformation . We now demonstrate that both of these agents inhibit the ras-p21 protein-induced maturation of Xenopus oocytes in a dose-related manner when microinjected into oocytes . The effects of each of these agents is specific . Both agents block insulin-induced maturation of oocytes, a process which is known to involve activation of endogenous normal p21 protein . On the other hand, neither agent inhibited oocyte maturation induced by progesterone, which is known to initiate oocyte maturation by ras-independent pathways . The inhibitory effects of the peptide were not mimicked by a control peptide from the CD4 receptor protein . Furthermore, the effect of azatyrosine was not mimicked by L-tyrosine . These results suggest that both the peptide and azatyrosine have potent anti-ras effects intracellularly.

Mol Gen Mikrobiol Virusol, 1991 Jul, (7), 25 - 8
{Cloning and inactivation of a chromosomal copy of the imidazole glycerophosphate dehydratase (HIS) gene from Hansenula polymorpha}; Semenova VD et al.; A gene for imidazole glycerophosphate dehydratase (HIS) has been selected from the library of Hansenula polymorpha genes by complementation of Escherichia coli hisB mutations or his3 mutation of Saccharomyces cerevisiae . Inactivation of the gene in Hansenula polymorpha strain 48V, as well as Leu(-)-Leu+ conversion of phenotype and arising of antibiotic G418 resistance resulted from transformation of the strain by the linear DNA molecules of the cloned HIS-gene with the in vitro inserted LEU2 gene from Saccharomices cerevisiae and KmR gene . The Southern hybridization analysis of the Leuf+His- G418R clones representing 1-2% of transformants population together with the DNA analysis of the monospore clones from the hybrid Leu+His-G418R transformant tetrad and tester strain have revealed the locus specific nature of the clones.

Ital J Gastroenterol, 1991 Jul-Aug, 23(6), 364 - 6
Prolonged viral hepatitis type A with cholestasis: case report; Schiraldi O et al.; We describe a clinical case of an eleven year old boy with a protracted cholestatic form of viral hepatitis type A . The role of a macrolide antibiotic in the determinism of this form of hepatitis is discussed.

J Biomol NMR, 1991 Jul, 1(2), 167 - 73
Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state NMR spectroscopy; Bechinger B et al.; Solid-state NMR spectroscopy was used to determine the orientations of two amphipathic helical peptides associated with lipid bilayers . A single spectral parameter provides sufficient orientational information for these peptides, which are known, from other methods, to be helical . The orientations of the peptides were determined using the 15N chemical shift observed for specifically labeled peptide sites . Magainin, an antibiotic peptide from frog skin, was found to lie in the plane of the bilayer . M2 delta, a helical segment of the nicotinic acetylcholine receptor, was found to span the membrane, perpendicular to the plane of the bilayer . These findings have important implications for the mechanisms of biological functions of these peptides.

Biochimie, 1991 Jul-Aug, 73(7-8), 1137 - 43
Chemical, biochemical and genetic endeavours characterizing the interaction of sparsomycin with the ribosome; Lazaro E et al.; Sparsomycin interaction with the ribosome and characteristics of the drug binding site in the particle were studied using chemical modification of the drug, affinity labeling methods and isolation of drug resistant mutants . The structure-function relationship studies, performed with a large number of drug derivatives, indicate that the drug interacts with the ribosome by its western and eastern moieties . The uracil ring, in the western end of the drug molecule, probably forms hydrogen bonds with the rRNA, while the apolar CH3-S-CH3 group in the eastern end interacts with a hydrophobic ribosomal domain that affinity labeling results seem to indicate is formed by protein . An increase in lipophilicity in this part of the antibiotic results in a dramatic increase in the inhibitory activity of the drug . The sparsomycin binding site is not accessible in free ribosomes, but the presence of an N-blocked amino acyl-tRNA at the P-site turns the particles capable of reversible interaction with the drug . After failure using Escherichia coli, a sparsomycin-resistant mutant was obtained by direct mutagenesis on Halobacterium halobium, a species with a unique copy of rRNA genes, stressing the role of rRNA on the drug interaction site.

Biochimie, 1991 Jul-Aug, 73(7-8), 1131 - 5
The binding of thiostrepton to 23S ribosomal RNA; Thompson J et al.; The antibiotic, thiostrepton, binds to 23S ribosomal RNA from E coli with a dissociation constant (KD) of 2.4 x 10(-7) M . The specificity of the interaction was established using 16S rRNA and modified or mutationally-altered 23S rRNA . Thus, no binding was detected with rRNA from the 30S subunit nor with rRNA modified in vitro by the thiostrepton resistance methylase . Mutant 23S rRNA, altered at residue 1067 in each of the 3 possible ways, showed reduced binding affinity for thiostrepton . The KD for the G mutation was 3.5 x 10(-6) M; for the C mutation, 2.4 x 10(-5) M; and for the U mutation, 4.8 x 10(-5) M . This reduction in drug binding is compatible with functional analyses; the C or U mutation results in ribosomal particles which are poorly inhibited by the drug compared with wild-type, whereas the G mutation results in an intermediate response to the drug in protein synthesis . The smallest 23S rRNA fragment used here that was capable of binding thiostrepton, in a nitrocellulose filter binding assay, comprised residues 1052-1112 and the dissociation constant was 3.0 x 10(-7) M, ie virtually indistinguishable from that with intact 23S RNA . However, the drug was incapable of binding to the 5'-moiety of this fragment (ie residues 1052-1084) or to an RNA transcript complementary to 1052-1112.

Mutat Res, 1991 Jul, 260(3), 265 - 9
Synergistic effect of CCNU and bleomycin on human lymphocytes exposed at late G1 and G2 states of the cell cycle; Koldamova RP et al.; The combined action of the antitumor antibiotic bleomycin and chloroethylnitrosourea (CCNU) was studied in human lymphocytes in vitro . All the experiments were carried out with 20 micrograms/ml bleomycin for a given treatment time . By adding 0.7 and 3.5 micrograms/ml CCNU at late G1-S phase we have demonstrated a considerable increase in both percent of aberrant cells and production of dicentrics and rings (5-fold, p less than 0.001) . At late S-G2 the combined treatment led to a significant enhancement of breaks per cell (p less than 0.0001) and cells with more than 12 aberrations . A possible explanation could be the known repair-inhibitory potential of CCNU, but its pure clastogenic action still has to be considered . The results presented here point out the need for seeking chemotherapeutic regimens with reduced concentrations of the drugs in combination.

J Gen Microbiol, 1991 Jul, 137 ( Pt 7), 1715 - 20
The effects of temperature, pH and growth rate on secondary metabolism in Streptomyces thermoviolaceus grown in a chemostat; James PD et al.; Streptomyces thermoviolaceus was grown in a chemostat under conditions of glutamate limitation . The effects of growth rate on production of the antibiotic granaticin, extracellular protein and protease activity as components of secondary metabolism were studied at 37, 45 and 50 degrees C . The amount of each secondary metabolite synthesized was highly dependent on growth rate and temperature . Granaticin yields were highest at growth rates of 0.1 to 0.15 h-1 at 37 degrees C, 0.175 h-1 at 45 degrees C and 0.045 h-1 at 50 degrees C . Protease activity of culture supernatants responded to low nutrient concentration and/or low growth rate . Measurements of extracellular protein revealed complex changes in amount which were dependent on growth rate and temperature . At 45 degrees C and a growth rate of 0.15 h-1, biomass yield was highest between pH 5.5 to 6.5 whereas granaticin synthesis was low at pH 5.5 and rose to highest values at between pH 6.5 and 7.5.

Virology, 1991 Jul, 183(1), 74 - 82
Synthesis of Semliki Forest virus RNA requires continuous lipid synthesis; Perez L et al.; The involvement of lipid biosynthesis in the replication of Semliki Forest virus (SFV) in HeLa cells has been analyzed by the use of cerulenin, an inhibitor of lipid synthesis . The presence of this agent from the beginning of infection blocks the appearance of viral proteins . However, when the antibiotic is added at later stages of infection it has no effect on protein synthesis, the cleavage of viral proteins and their acylation by palmitic acid . Cerulenin is a powerful inhibitor of viral RNA synthesis, as analyzed by {3H}uridine incorporation, incorporation of {32P}phosphate into viral replication complexes, or Northern blot analysis of viral RNAs hybridized with minus- or plus-stranded riboprobes . Finally, analysis of phospholipids made in SFV-infected cells indicates that viral infection clearly stimulates the synthesis of phosphatidyl choline and modifies the membrane formed as analyzed by sucrose gradient centrifugation . Cerulenin blocks the synthesis of phospholipids and inhibits the formation of new membranes . These results show that, when the synthesis of lipids is blocked by cerulenin, SFV RNA replication is hampered, suggesting that the synthesis of viral RNAs needs continuous lipid synthesis and membrane formation.

Gene, 1991 Jun 30, 102(2), 265 - 9
A pair of selectable herpesvirus vectors for simultaneous gene expression in human lymphoid cells; Alt M et al.; The genome of Herpesvirus saimiri, a lymphotropic virus of non-human primates, was used to develop a vector system for transducing foreign genes into primary human T-cells and T-lymphoid cell lines . Recombinant viruses were obtained by homologous recombination of the viral genome with linearized plasmid DNA . The plasmid used contained a fragment of virion DNA, a hygromycin-B-resistance marker (HyR), and a multiple cloning site for the insertion of additional expression cassettes . The resulting recombinants were efficiently enriched and were plaque-purified . The virus mediating HyR and a H . saimiri strain carrying the Geneticin-resistance marker were used to infect the human T-lymphoid cell line Jurkat . Lymphocytes with a double-resistant phenotype were shown to contain the two different H . saimiri recombinants persisting as episomes at high multiplicity . The H . saimiri vector system will be suitable to study cooperating regulatory genes in T-lymphocytes.

N Engl J Med, 1991 Jun 20, 324(25), 1773 - 8
Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer; Nemunaitis J et al.; BACKGROUND . The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality . The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation . METHODS . We conducted a randomized, double-blind, placebo-controlled trial at three institutions . The study design and treatment schedules were identical, and the results were pooled for analysis . One hundred twenty-eight patients were enrolled . Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo . RESULTS . No toxic effects specifically ascribed to rhGM-CSF were observed . The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs . 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs . 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs . 33 days; P = 0.01) . There was no difference in the survival rate at day 100 . CONCLUSIONS . In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity . Further studies will be required to establish its optimal dosage and schedule of administration.

Biochim Biophys Acta, 1991 Jun 18, 1065(2), 160 - 6
Incorporation of synthetic peptide helices in membranes of tetraether lipids from Thermoplasma acidophilum . A calorimetric study; Blocher D et al.; Four analogues of the membrane-modifying, alpha-helical polypeptide antibiotic alamethicin were synthesized . the alpha-helical deca-, undeca-, heptadeca-, and icosapeptides were mixed with the main tetraether lipid of the Archaebacterium Thermoplasma acidophilum (MPL), dipalmitoylphosphatidylcholine (DPPC) and dihexadecylmaltosylglycerol (DHMG) in various ratios and the modification of the lipid phase transition was determined by differential thermal analysis (DTA) . The polypeptides form mixed phases with MPL and DPPC, however, not with DHMG . Heptadeca- and icosapeptide exert a much stronger reduction of enthalpy (delta H) than deca- and undecapeptide and bind about 0.5 molecule of MPL (or one molecule of DPPC) per peptide molecule . delta H of the DPPC pretransition is reduced by the deca- and the undecapeptides and completely disappears with heptadeca- and icosapeptides (at 0.2 mole of peptide/mole of lipid) . The modulation of the melting point Tm by the incorporation of peptides is more pronounced with MPL than with DPPC, the heptadecapeptide exhibiting the strongest reduction (with MPL) and the strongest broadening of the transition peak (with DPPC) . Helix length, amphiphilicity and charge of the polypeptides can be correlated with the observed modifications of the lipid phase transitions.

Biochemistry, 1991 Jun 18, 30(24), 5838 - 45
Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus; Yamashita Y et al.; Saintopin is an antitumor antibiotic recently discovered in mechanistically oriented screening using purified calf thymus DNA topoisomerases . Saintopin induced topoisomerase I mediated DNA cleavage comparable to that of camptothecin, and topoisomerase II mediated DNA cleavage equipotent to those of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) or 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) (VP-16) . Treatment of a reaction mixture containing saintopin and topoisomerase I or II with either elevated temperature (65 degrees C) or higher salt concentration (0.5 M NaCl) resulted in a substantial reduction in DNA cleavage, suggesting that the topoisomerase I and II mediated DNA cleavage induced by saintopin is through the mechanism of stabilizing the reversible enzyme-DNA "cleavable complex" . Consistent with the cleavable complex formation with both topoisomerases, saintopin inhibited catalytic activities of both topoisomerase I and topoisomerase II . The DNA cleavage intensity pattern induced by saintopin with topoisomerase I was different from that by camptothecin . A difference in cleavage pattern was also detected between saintopin and m-AMSA or VP-16 in topoisomerase II mediated DNA cleavage . DNA unwinding assay using T4 DNA ligase showed that saintopin is a weak DNA intercalator like m-AMSA . Thus, saintopin represents a new class of antitumor agent that can induce both mammalian DNA topoisomerase I and mammalian DNA topisomerase II mediated DNA cleavage.

Ann Intern Med, 1991 Jun 15, 114(12), 1005 - 9
Serologic response to treatment of infectious syphilis; Romanowski B et al.; OBJECTIVE: To evaluate the serologic response to treatment of patients with infectious syphilis . DESIGN: Historical cohort study of all cases of infectious syphilis in Alberta from 1981 to 1987 . PATIENTS: A total of 1090 patients were entered; 857 with primary syphilis, 183 with secondary syphilis, and 50 with early latent disease . Two hundred and eight patients were excluded who either were pregnant, had negative serologic results before treatment, had clinical relapse, were treatment failures, or were lost to follow-up . INTERVENTIONS: All 882 evaluable patients were treated with a recommended antibiotic regimen for infectious syphilis and returned for re-assessment including repeat serologic testing . MEASUREMENTS AND MAIN RESULTS: Seventy-two percent (95% CI, 66% to 77%) and 56% (CI, 43% to 70%) of patients with initial episodes of primary or secondary syphilis had seroreverted according to rapid plasma reagin (RPR) test results by 36 months . A 2- and 3-tube decline was seen by 6 and 12 months in primary and secondary syphilis . Early latent syphilis resulted in only a 2-tube decrease at 12 months . Serologic response was not affected by sex, age, race, or sexual orientation . Patients with their first infection were more likely to experience RPR seroreversal than those with repeat infections . The RPR reversal rates also depended on the pretreatment titer and stage of disease . At 36 months, 24% (CI, 20% to 28%) of patients had nonreactive fluorescent treponemal antibody absorption tests (FTA-Abs), and 13% (CI, 11% to 15%) had nonreactive microhemoglutination tests for Treponema pallidum (MHA-TP) . CONCLUSIONS: Adequate therapeutic response for syphilis must be based on illness episode and the pretreatment RPR titer . Treponemal tests can demonstrate seroreversion after 36 months, and a negative treponemal test does not rule out a past history of syphilis.

Cancer, 1991 Jun 15, 67(12), 2969 - 73
Cisplatin and novobiocin in the treatment of non-small cell lung cancer . A Southwest Oncology Group study; Ellis GK et al.; Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin . Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin) . One patient remains on study and cannot be evaluated for response . No complete responses were seen . Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response . The median survival time of all patients was just less than 7 months . These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC) . Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity . It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.

Biochemistry, 1991 Jun 11, 30(23), 5707 - 15
One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium; Bolard J et al.; The inducement of K+ permeability through membranes by the polyene antibiotic amphotericin B (AmB) has been analyzed as a measure of the antibiotic activity . Dose-response curves have been obtained with cholesterol- and ergosterol-containing egg yolk phosphatidylcholine large unilamellar vesicles (LUVs), human erythrocytes, and Saccharomyces cerevisiae cells . Conductance changes induced by AmB in sterol-containing planar bilayer membranes have also been studied . AmB self-association in aqueous buffer was determined by circular dichroism (CD) as a function of the antibiotic concentration . Electronic absorption and CD spectra of AmB were recorded in the presence of LUVs . For given AmB concentrations, the extent of permeability inducement is dependent on the lipid concentration . On the other hand, for cholesterol-containing LUVs or erythrocytes, a critical AmB concentration had to be reached before any permeability is observed . Independent of lipid concentration, this concentration was directly related to antibiotic self-association in the aqueous buffer . The same observation was made for erythrocytes and nystatin . The AmB absorption and CD spectra were totally different for ergosterol- and cholesterol-containing LUVs . Formation of single channels by one-sided addition of AmB could be observed only in ergosterol-containing membranes . These data lead us to propose that the permeability pathways induced by amphotericin B or nystatin, in ergosterol- and in cholesterol-containing membranes, are of different natures . In the latter case the antibiotics are only active, by single-sided addition, in the self-associated form . These findings offer important clues for the design of less toxic derivatives of AmB: they should have a low degree of self-association in water.

Top Hosp Pharm Manage, 1991 Jul, 11(2), 79 - 89
A survey of current operations and future plans for ambulatory pharmacy services; Powell MF et al.; Survey results indicate that the number of hospital-based ambulatory pharmacies in the survey area is increasing substantially . By the end of 1989, there would have been a 71 percent increase in the number of hospitals providing ambulatory pharmacy services in this region . This assumes that those hospitals in the planning stages of developing ambulatory pharmacy services completed their plans . While the number of hospital-based ambulatory pharmacies is on the rise, there has been a concurrent increase in the number of services provided by the pharmacies already in operation . There has been a 38 percent increase in the number of services provided by these pharmacies since the inception of DRGs . The services that have been added are primarily specialized services including home TPN compounding, intravenous antibiotic compounding, intravenous chemotherapy compounding, medical supplies, and durable medical equipment . It is likely that these services will continue to increase in the coming years as home therapies continue to become more advanced . The study also indicates that most hospital-based ambulatory pharmacies in this region are operated as nonprofit entities . A trend toward for-profit pharmacy operations was anticipated, and this is still anticipated as more ambulatory pharmacy operations become separate entities from inpatient services . Future studies of this type should monitor this possible trend . Most hospital-based ambulatory pharmacies are owned by the hospital or a hospital affiliate . More than half of respondents reported their ambulatory pharmacies are located within the inpatient pharmacy of the hospital . As the trend toward separate ambulatory pharmacy operations increases, it would not be unusual for the pharmacies to be operated by for-profit affiliates of the hospital or outside contractors . Barker predicts that hospital-based ambulatory pharmacies could become units of major drug store chains in the future . This is another area that is worthy of future studies of hospital-based ambulatory pharmacy operations . Overall, the results of this study indicate that hospitals in this region have not remained static since the inception of DRGs . There seems to be a dynamic period of change evolving in the delivery of health care services in this region . The demographic section of this study reveals that the majority (more than 70 percent) of the hospitals surveyed are operating fewer numbers of beds for inpatient services since ther inception of DRGs . The length of time that patients remain in the hospital for inpatient services is decreasing, resulting in decreased demand for inpatient beds.(ABSTRACT TRUNCATED AT 400 WORDS)

South Med J, 1991 Jun, 84(6), 733 - 5, 739
Oral candidiasis as a marker of acute retroviral illness; Dull JS et al.; All reported clinical characteristics of acute retroviral illness with the human immunodeficiency virus (HIV) are nonspecific . Signs and symptoms described are associated with a variety of acute infections . We report the cases of three patients in whom the acute retroviral illness was characterized by transient oral candidiasis and unexplained high lactate dehydrogenase values, with or without transient pulmonary infiltrate, in the context of an acute febrile illness . The clinical findings correlated with a severe reduction in the number of CD4 cells . We believe that thrush could be a marker of acute retroviral infection, as it is not a feature of any other heterophil-negative mononucleosis-like syndrome . We propose that in any patient having transient thrush and acute viral syndrome, the possibility of HIV infection should be aggressively pursued serologically, regardless of the patient's HIV risk status, provided that the usual causes of candidiasis (eg, diabetes mellitus, antibiotic use, and dentures) can be excluded.

Am Rev Respir Dis, 1991 Jun, 143(6), 1408 - 11
Pseudomembranous tracheobronchitis caused by Aspergillus; Hines DW et al.; Four immunosuppressed patients with a rapidly evolving, febrile, respiratory distress syndrome were found at autopsy to have Aspergillus pseudomembranes of their lower tracheobronchial tree . Steroids, neutropenia, broad spectrum antibiotic use, and alcoholism appear to be predisposing risk factors . Bronchoscopy may reveal the pathology but antemortem diagnosis is difficult because of the low yield of sputum cultures and fulminant nature of the disease.

Toxicol Lett, 1991 Jun, 57(1), 1 - 9
Central effects of cycloheximide alone and of its combination with T-2 toxin; Bergmann F et al.; The antibiotic cycloheximide inhibits protein synthesis in eukaryotic cells . This overall effect is similar to that of T-2 toxin, but the mechanism of intoxication by these two inhibitors are different . This is shown here by intracerebral injections of mixtures of T-2 toxin and cycloheximide, leading to potentiation of their toxic effects . The histopathology of cerebral intoxication by the two compounds is similar, but after cycloheximide the lesions appear earlier, and repair is faster.

J Bacteriol, 1991 Jun, 173(11), 3408 - 13
The Escherichia coli hemL gene encodes glutamate 1-semialdehyde aminotransferase; Ilag LL et al.; delta-Aminolevulinic acid (ALA), the first committed precursor of porphyrin biosynthesis, is formed in Escherichia coli by the C5 pathway in a three-step, tRNA-dependent transformation from glutamate . The first two enzymes of this pathway, glutamyl-tRNA synthetase and Glu-tRNA reductase, are known in E . coli (J . Lapointe and D . Soll, J . Biol . Chem . 247:4966-4974, 1972; D . Jahn, U . Michelsen, and D . Soll, J . Biol . Chem . 266:2542-2548, 1991) . Here we present the mapping and cloning of the gene for the third enzyme, glutamate 1-semialdehyde (GSA) aminotransferase, and an initial characterization of the purified enzyme . Ethylmethane sulfonate-induced mutants of E . coli AB354 which required ALA for growth were isolated by selection for respiration-defective strains resistant to the aminoglycoside antibiotic kanamycin . Two mutations were mapped to min 4 at a locus named hemL . Map positions and resulting phenotypes suggest that hemL may be identical with the earlier described porphyrin biosynthesis mutation popC . Complementation of the auxotrophic phenotype by wild-type DNA from the corresponding clone pLC4-43 of the Clarke-Carbon bank (L . Clarke and J . Carbon, Cell 9:91-99, 1976) allowed the isolation of the gene . Physical mapping showed that hemL mapped clockwise next to fhuB . The hemL gene product was overexpressed and purified to apparent homogeneity . The pure protein efficiently converted GSA to ALA . The reaction was stimulated by the addition of pyridoxal 5' -phosphate or pyridoxamine 5' -phosphate and inhibited by gabaculine or aminooxyacetic acid . The molecular mass of the purified GSA aminotransferase under denaturing conditions was 40,000 Da, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The enzyme has apparent native molecular mass of approximately 80,000 Da, as determined by rate zonal sedimentation on glycerol gradients and molecular sieving through Superose 12, which indicates a homodimeric alpha2, structure of the protein.

J Parasitol, 1991 Jun, 77(3), 505 - 8
Axenic isolation of viable Giardia muris trophozoites; Tillotson KD et al.; Large numbers of viable Giardia muris trophozoites were isolated from the duodenum of experimentally infected mice 6 days after inoculation with 1,000 G . muris cysts . A series of shaking, incubation, and washing steps in the presence of the broad-spectrum antibiotic piperacillin readily provided 4.9 +/- 1.5 x 10(5) G . muris trophozoites per mouse, free of detectable contaminant organisms . Anaerobic and microaerophilic culturing and scanning electron microscopy demonstrated axenic status and high purity of the isolates . The viability of trophozoites was 98 +/- 2% . Application of this technique should permit novel immunological and epidemiological analyses of G . muris infection and biochemical investigations of this protozoan parasite.

Postgrad Med, 1991 Jun, 89(8), 237 - 40, 243-4
Lower limb problems in diabetic patients . What are the causes? What are the remedies?
Bell DS.
Peripheral neuropathy, infection, and peripheral vascular disease can produce serious problems in diabetic patients, particularly in the lower limbs . Ulceration of the foot may progress to gangrene and ultimately necessitate amputation . Distal symmetric polyneuropathy causes sensory loss . Such loss in patients with peripheral vascular disease creates a high risk for foot ulcers, which are vulnerable to infection . Treatment includes relief of neuropathic pain and antibiotic therapy for infection . Pentoxifylline (Trental) improves microvascular flow and appears to be effective against peripheral vascular disease . Aldose reductase inhibitors are being investigated as therapy for diabetic neuropathy . Prevention is the mainstay of management in these patients . Patient education is essential to help maintain health and prevent the potential adverse effects of diabetes.

J Clin Oncol, 1991 Jun, 9(6), 1022 - 8
Therapeutic effects and pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy; Furman WL et al.; Twenty-five children with refractory solid tumors were given recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in escalated doses of 60 to 1,500 micrograms/m2 as 2-hour intravenous infusions, beginning 24 hours after myelosuppressive treatment with cisplatin and etoposide . Tolerance to rhGM-CSF was exceptional even at dose levels that exceeded the maximum-tolerated dosage (MTD) reported for adults . The agent produced dose-related increases in platelet and neutrophil counts, resulting in significantly shorter durations of severe neutropenia and thrombocytopenia (P less than .01 for each analysis) . At the higher dosages (greater than or equal to 750 micrograms/m2), treatment with rhGM-CSF reduced the median number of days of antibiotic therapy for fever and neutropenia by approximately one half . We conclude that rhGM-CSF is well tolerated by leukopenic children in doses as high as 1,500 micrograms/m2 . An MTD was not reached in this study . The ability of the growth factor to reduce severe neutropenia and thrombocytopenia suggests it will have an important role in the management of childhood solid tumors.

Rev Esp Cardiol, 1991 Jun-Jul, 44(6), 408 - 10
{Aortic valve replacement by a pulmonary homograft}; Mestres CA et al.; Minor experience still exists in our country with regard to the use of valve homografts in cardiac surgery . Only a few implantations have been performed in cases of right ventricular outflow tract reconstruction in addition to our own experience in cases of infective endocarditis of the aortic valve . We present a case of aortic valve replacement by using an antibiotic-sterilized fresh pulmonary valve autograft . The case is described and the possible advantages of the use of pulmonary allografts in the aortic position are discussed.

Lymphology, 1991 Jun, 24(2), 68 - 70
Lymphedema of the leg associated with rheumatoid arthritis; Lacroix HR et al.; A 14-year-old boy with a two year history of seronegative rheumatoid arthritis developed left leg lymphedema and subsequently a severe episode of lymphangitis . The diagnosis of "rheumatoid lymphedema" was confirmed by lymphscintigraphy and conventional lymphography . Treatment consisted of bedrest and antibiotic drugs . When the signs of inflammation had subsided, therapy with corticosteroids was started with improvement of both joint pain and leg swelling . Whereas lymphedema associated with rheumatoid arthritis has been described in the upper limb of adults, to our knowledge this is the first report of the coexistent condition in the lower leg of a child.

Am J Infect Control, 1991 Jun, 19(3), 143 - 6
Prevalence of nosocomial infection in long-term-care Veterans Administration medical centers; Steinmiller AM et al.; Prevention and control of nosocomial infections are major goals of institutional risk-management programs . However, variations in criteria and denominator parameters make comparison of rates across settings difficult . This study addressed those problems by reporting criteria used to identify infections and applying the same denominator across long-term-care facilities . Findings demonstrated a 9.8% prevalence rate for nosocomial infections in four long-term-care VA facilities . Most of the identified infections were consistent with Centers for Disease Control definitions of nosocomial infections . The most frequent indicators of nosocomial infections that did not fully meet those definitions were (1) documented symptoms, (2) antibiotic therapy, and (3) physician diagnosis.

Am J Surg, 1991 Jun, 161(6), 693 - 701
Treatment of compound fractures; Seligson D et al.; Management of compound fractures remains a challenge to the surgeon . Methods to decrease patient morbidity include early fracture stabilization and sequential debridement . External fixation remains the standard; however, early internal fixation in low-grade injuries may be an acceptable option . Early soft tissue coverage is critical . The use of prophylactic parenteral antibiotics has decreased the incidence of acute infection and chronic osteomyelitis . Supplemental use of local antibiotic polymethyl methacrylate (PMMA) beads appears to further diminish the morbidity in high-grade open fractures.

Infect Immun, 1991 Jun, 59(6), 2012 - 6
Memory T cell-mediated resistance to Mycobacterium tuberculosis infection in innately susceptible and resistant mice; Hubbard RD et al.; The memory T cell immune response to Mycobacterium tuberculosis infection was examined in strains of mice which vary in their natural susceptibility to Mycobacterium bovis BCG infection . Naturally susceptible (NS) C57BL/6 and naturally resistant (NR) B6D2 F1 hybrid mice were infected with a sublethal dose of M . tuberculosis and then given antibiotic therapy beginning 2 weeks postinfection . T cells from both strains of mice transferred significant levels of resistance to syngeneic mice challenged aerogenically with M . tuberculosis . This memory response was not substantially reduced by depletion of either L3T4+ or Lyt2+ T cells from the donor mice but was ablated by depletion of both T cell subsets . Cyclophosphamide pretreatment of C57BL/6 memory T cell donors also ablated the resistance transferred to recipient mice . In contrast, B6D2 memory T cells were not affected by cyclophosphamide treatment, suggesting that differences may exist in the metabolic state of the memory T cells in the two donor strains, despite the fact that they both develop similar levels of acquired resistance to a subsequent tuberculous challenge.

Antibiot Khimioter, 1991 Jun, 36(6), 48 - 50
{The comparative pharmacokinetics of ceftriaxone in the blood and bronchial secretion in patients with different durations in the course of chronic bronchitis}; Kamnev IuV et al.; The study on ceftriaxone penetration into bronchial secretion showed that in patients with a short-term history of chronic bronchitis (no more than 3 years) ceftriaxone used in a dose of 1 g once a day intramuscularly was detectable in the bronchial secretion within 10 hours after the administration, its concentrations being 0.67-2.41 micrograms/ml in 3 hours, 15.87 micrograms/ml in 4.5 hours, 4.58 micrograms/ml in 6.5 hours and 2.29 micrograms/ml in 10 hours . In patients with a long-term history of chronic bronchitis (mean 10 to 20 years) the presence of ceftriaxone in the bronchial secretion was detectable in a concentration of 0.51-3.75 micrograms/ml only in 2 hours after its administration . Beginning from the 5th hour after the administration its detection failed . This is indicative of lower ceftriaxone penetration into the bronchial secretion of such patients . The duration of chronic bronchitis did not influence ceftriaxone pharmacokinetics in blood . The contents of the antibiotic in serum and bronchial secretion were determined by HPLC (the resolving power of 0.5 micrograms/ml).

Rev Rhum Mal Osteoartic, 1991 Jun, 58(6), 433 - 9
{Bacillary trochanteritis . Apropos of 30 cases}; Franceschi JP et al.; Tuberculous trochanteritis is rare . The authors report 30 cases, 2/3 of which were seen in sanatoria . They occurred in four cases out of five in patients with long standing tuberculosis but were sometimes the presenting feature . Development of an abscess of the trochanteric serous bursa is a virtually constant complication . Their minimal functional consequences and slow progression endow them with an apparently benign nature which masks the risk of secondary complications (4 cases of coxalgia) . Radiological appearances, minimal in early forms, are currently becoming more abundant by virtue of new medical imaging techniques . Specific antibiotic therapy is adequate in two cases out of three, completed in advanced and aggressive forms by local procedures dominated by surgical excision (13 cases).

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