Depress Anxiety, 1996-97, 4(3), 139 - 43 Hoigne's syndrome, kindling, and panic disorder; Araszkiewicz A et al.; A review of Hoigne's syndrome (HS) is presented, and 47 cases of putative procaine penicillin-induced HS are discussed within the context of kindling models of human psychopathology . Sixty percent of the individuals with HS in our retrospective study reported a lifetime history of panic disorder . The risk factors and causal relationships among repeated injection of procaine penicillin, HS, and anxiety disorders, particularly panic disorder, require further investigation. Neurochirurgie, 1996, 42(3), 153 - 61 {Multiple cortical photolesions and penicillin epileptogenic focus . Study of a model in rabbits}; Devaux B et al.; Inactivation of an epileptogenic focus by dividing it into sub-unities unable to maintain epileptic activity has been demonstrated in animals . Based on these experiments, multiple subpial transections have been performed in patients suffering from partial drug-resistant epilepsies when resection of the epileptogenic cortex was not possible . In order to develop a new surgical technique for such epilepsies, the authors present an initial study of multiple cortical laser photolesions on the rabbit brain . The aim of this study is to assess the histological lesions created on the cortex with a laser at a chronic stage, and to compare the electrical paroxysmal activity of a penicillin focus on the laser irradiated cortex and on the non radiated cortex in the same animal . Twenty-five adult albino rabbits were used for this study . Both hemispheres of 19 rabbits have been exposed; 14 to 35 photolesions in a network were performed on one hemisphere using a 1.064 microns wavelength Nd-YAG laser . Six to twenty-one days later, a penicillin-induced focus was created on both hemispheres, a corticographic study was performed, and each animal was sacrificed for histological study of the brain . For the 6 last animals a high-power 0.805 micron wavelength diode laser was used with the same protocol . Histological study was solely performed in order to compare the effects of both lasers . In 11 animals electrocorticographic control was reliable . Time to first spike occurrence after penicillin application was significantly increased on the treated hemisphere as compared to the untreated one (1' to 14'30" and 10" to 6', respectively; p < 0.01) and the number of spikes per minute at early and late counts was significantly smaller on the treated hemisphere as compared to the untreated one (1 to 29 and 2 to 70, respectively; p < 0.02) . Histologically the lesions appeared as cone-shaped coagulation necrosis surrounded by an area of macrophagic reaction, angiogenesis and gliosis . With the diode laser, some lesions included ischemic changes extended in the white matter . This study demonstrated the possibility of creating limited and reproducible photolesions using the laser light energy, without extensive destruction of the cortex . These lesions were reaching from one third to the totality of the cortical depth, depending on laser exposure parameters . This study also demonstrated that these photolesions arranged in a network and at a chronic stage were associated with a significantly reduced paroxysmal activity of a penicillin focus when compared to intact cortex . Since such lesions did not totally isolate cortical sub-unities, spiking was still recorded from the irradiated cortex, but at a lower rate, suggesting a disorganization of the local neuronal network responsible for paroxysmal activity. Acta Vet Scand, 1996, 37(4), 453 - 60 The influence of tail biting on performance of fattening pigs; Wallgren P et al.; In comparison to 29 non bitten animals, severe tail biting was found to decrease the daily weight gain (DWG) by 25% in 8 fattening pigs during the period of biting . However, when comparing the weight gain of the lifetime between bitten and non bitten pigs, no influence of the tail biting was found . It is of interest that severely wounded pigs were parenterally treated with prokainpenicillin G for 3 consecutive days in connection with the tail biting, which could be suggested to promote the growth by reducing the influence of infections gained by the tail biting as well as of other infections present in herds rearing conventional pigs . Despite penicillin treatment, abscesses were more frequently recorded in tail bitten pigs than in non bitten animals . The tail biting was not equally distributed between the sexes, as barrows were more frequently bitten than gilts . Among the unbitten pigs, barrows were also found to grow faster than gilts . Indeed, when comparing tail bitten and non bitten barrows, a negative influence of tail biting on DWG was not only shown during the period of biting, but could also be monitored as a reduced DWG from that period until slaughter by 11% and during lifetime by 5% (the tail bitten gilts were too few to allow statistical calculations) . These results clearly indicate that tail biting affects the growth rate of the lifetime despite penicillin treatment . However, it should be stressed that this decreased lifetime DWG may not be monitored when evaluating abattoir data because the sex distribution of the pigs may not be known in such materials. Aviakosm Ekolog Med, 1996, 30(4), 40 - 4 {Role of hypoxia in the development of epileptiform seizures}; Agadzhanian NA et al.; The article reviews the factors of abiotic and biotic environments liable to provoke convulsions . An assumption is made that the common element of their action on the organism are hypoxic states of varying types and depth . Animals with high individual tolerance of acute hypoxia were found to possess a better resistance to the convulsing effect of penicillin . In these animals the epilepsy-form discharges appear with longer latent periods and the epilepsy-form seizures are generated much more seldom in contrast to rats with poor tolerance of hypoxia . Training of resistless rats in the altitude chamber increases their ability to oppose the convulsing effect of penicillin to the level of animals with moderate but not high hypoxia tolerance. Mycopathologia, 1996, 134(3), 115 - 20 Synergy of human neutrophils with fluconazole in killing Candida species; Brummer E et al.; The killing of Candida species by human neutrophils in a long-term 24-h assay and possible synergy with fluconazole (FCZ) for killing was investigated . The test medium (TM) consisted of RPMI-1640, penicillin and streptomycin (P/S), and 10% fresh autologous serum . TM alone was highly fungistatic for Candida species compared to TM without serum . When neutrophils were cocultured in TM with Candida species for 24 h the inoculum colony-forming units (CFU) were always significantly reduced (killing) by 58 to 99% . FCZ was tested over a range of 1-500 micrograms/ml, and though almost always fungistatic itself, it synergized with neutrophils for significantly increased killing of C . albicans (isolate Sh27) (P < 0.01) and C . albicans (isolate 94-20) (P < 0.05) . Killing of non-albicans Candida species was so efficient in the absence of FCZ that demonstration of synergy with FCZ was difficult. Przegl Epidemiol, 1996, 50(3), 273 - 9 {Mucocutaneous lymph node syndrome (Kawasaki disease) in 2 children}; Szychowska Z et al.; Two children with Kawasaki disease (KD), a girl 3 yrs . and a boy 2.5 yrs., were described . The children met all criteria for the diagnosis of KD (fever, conjunctivitis, oral changes, extremity changes, rash, lymphadenopathy), and other diseases were excluded . In both children or one of them other clinical and laboratory findings occasionally detected in KD were observed: arthralgia, hepatomegaly and splenomegaly, slight elevation of transaminases and bilirubin level, slight elevation of CSF pleocytosis, sterile pyuria and hematuria . Electrocardiograms revealed sinus tachycardia and transient disturbances of heart repolarization . In both children changes in blood morphology and biochemical disturbances typical for inflammatory processes were noted . Thrombocytosis was seen in the 2nd week of the illness in the child in whom platelet counts were controlled . The child in whom diagnosis of KD was established in the first week of symptoms was treated with acetylsalicylic acid along with an oral penicillin . A child with retrospectively diagnosed KD was treated with antibiotics and corticosteroids . Clinical and laboratory findings of KD resolved in both children within 4-6 weeks without complications from coronary blood vessels. Acta Neurobiol Exp (Wars), 1996, 56(3), 673 - 81 The influence of repeated systemic penicillin injections at subconvulsive doses on spontaneous spike-wave discharges in the rat; Stankiewicz J et al.; Changes in nonconvulsive spontaneous epileptic activity-Spike-Wave Discharges (SWD)-induced by repeated intraperitoneal (i.p.) administration of crystalline penicillin (PC) at subconvulsive doses were evaluated in imp-DAK rats . Three groups received ten daily i.p . injections of PC at doses of 750,000, 500,000 and 250,000 IU/kg b.w . For comparison, another classic convulsant, pentylenetrazol (PTZ) was applied in the same way to another group . PTZ was also given to all rats before and after injection series for better evaluation of changes in CNS excitability . Repeated PC injections resulted in a progressive increase in the basal level of the spontaneous SWD activity and in an increase in the SWD response to PC, which was statistically significant in the case of the dose 750,000 IU/kg . Moreover, in all rats given PC the response to PTZ (increase in SWD activity) was reduced . The results obtained in this and previous experiment suggest that in the course of repeated systemic Pc administration adaptive changes in the rat CNS develop which prevent the convulsive effects of Pc but promote the occurrence of the spontaneous nonconvulsive SWD activity. Med Law, 1996, 15(2), 277 - 82 Ethical considerations in rural health nursing; Stark R; Nurses are the health workers most frequently found providing primary health care services in rural communities throughout the world . In these settings, often with limited resources and far from professional support systems, nurses may encounter ethical dilemmas quite different from those experienced by their colleagues in urban hospital settings . Consider the following example from a remote island community . A young nurse with two years experience in an urban hospital is posted to a remote village . In this country there are very few doctors, so nurses diagnose and treat common health problems . On this day a traditional political leader, a middle-age man, is brought to the small clinic by his adult son to be treated for his cough . Other patients are waiting to be seen, but the son makes it clear that he expects his father to be cared for immediately . The nurse doesn't think it is right to give preferential treatment, but the other patients back away and she defers to the son's demands . The nurse examines the man and concludes that he has a common viral infection requiring only symptomatic treatment . When she tries explaining this to the patient, he becomes annoyed and insists that what he needs is a penicillin injection . That's how the last nurse working in this clinic had treated him when he was sick and he had recovered within days . Finally, the young nurse overwhelmed by his age and status and under pressure from his family gives the injection . Shortly afterwards the patient collapses in shock and very nearly dies . The family blamed the nurse, and the community council demanded that she be removed . The case was eventually investigated by the authorities, and the nurse was formally reprimanded for giving the patient an unnecessary injection which caused him harm . Rural nurses-indeed all rural health workers-need support in order to maintain ethical standards in practice . The purpose of this paper is to examine four potential sources of such support: nursing education programs; the Ministries of Health; the law; and the professional nursing organization. Int J Clin Lab Res, 1996, 26(2), 112 - 8 Phagocyte chemiluminescence in pre-term infants; Pierce LA et al.; Intact phagocyte function is a pre-requisite for successful defence against infection, but paradoxically, these cells may also play a major role in the pathogenesis of the infant respiratory distress syndrome . Phagocyte function is known to be deficient in pre-term infants, who are at risk of infection as a result, but these infants are also at risk of respiratory distress syndrome as a result of surfactant deficiency . Despite this, few longitudinal studies of phagocyte function have been performed in pre-term infants . We have used lucigenin-enhanced chemiluminescence to examine the respiratory burst of mixed samples containing polymorphonuclear leucocytes and monocytes of 100 pre-term infants at 48- to 72-h intervals during their admission to a neonatal care unit . Increased polymorphonuclear leucocyte chemiluminescence was associated with respiratory distress syndrome and the use of intermittent positive pressure ventilation . Multiple linear regression analysis revealed a slight, but significant depression of chemiluminescence in association with the use of gentamicin and penicillin when stronger influencing factors such as the presence of respiratory distress syndrome were taken into consideration . Measurement of phagocyte function by sensitive luminescence assays requires very little blood and may be useful in pre-term infants to follow the severity of respiratory distress syndrome . However, it is probable that other factors such as antioxidant capacity also have an important influence on the degree of tissue damage. Arch Toxicol, 1996, 70(5), 284 - 92 Cisplatin-induced toxicity in immortalized renal cell lines established from transgenic mice harboring temperature sensitive SV40 large T-antigen gene; Hosoyamada M et al.; We established renal cell lines from definite nephron segments which were microdissected from kidneys of transgenic C57BL/6 mice, harboring the large T-antigen gene of temperature-sensitive mutant simian virus 40, pSVtsA58(ori-) . Cell culture was under a humidified atmosphere of 5% CO2 in air, on collagen-coated dishes, and in RITC80-7 medium with 5% fetal bovine serum, 10 micrograms/ml transferrin, 1 microgram/ml insulin, 10 ng/ml recombinant human EGF, penicillin and streptomycin . Cell line which kept contact inhibition character was established from each segment . Cells derived from distal tubule, cortical and outer medullary collecting duct possessed their cyclic AMP response to arginine-vasopressin, like their original nephron segment . On the other hand, cells derived from terminal proximal tubules (S3 segment) formed a cobblestone-like confluent monolayer, and did not respond to arginine-vasopressin like their fresh segments . Since cisplatin, a well-known nephrotoxic substance, damages proximal tubules (especially S3) rather than collecting ducts, we assayed cell number, protein content, and ATP content of cultured S3 cells at various times after addition of 0.2 mM cisplatin . Decrease of cell number, total protein content and total ATP content of culture cells occurred after 10 h incubation with 0.2 mM cisplatin . The 50% lethal dose (LD50) of cisplatin in S3 cells was 4 x 10(-5) M after 20 h incubation and 8.5 x 10(-6) M after 40 h incubation . Outer medullary collecting duct (OMCD) cells were damaged 30% maximally after 20 h incubation with cisplatin, and LD50 in them became 2.5 x 10(-5) M after 40 h incubation . We could show that the LD50 of cisplatin in the OMCD cell line was three times higher than that in the S3 cell line . Thus, these cell lines are the first in the kidney to definite the segmental origin and to maintain some differentiated unique functions . They are valuable for studies on intrarenal site-specific actions and possible mechanisms of action of pharmacological and toxic substances. Infection, 1996 Jan-Feb, 24(1), 85 - 7 Success and failure in the treatment of acrodermatitis chronica atrophicans; Aberer E et al.; To determine the most effective treatment for acrodermatitis chronica atrophicans, several clinical trials were undertaken in recent years to evaluate whether a 2-week course of ceftriaxone would be superior to oral antibiotics . Of the 46 patients suffering from acrodermatitis chronica atrophicans, 14 were treated with ceftriaxone 2g for 15 days . The remaining patients received either oral penicillin V 1.5 million IU t.i.d . or doxycycline 100 mg b.i.d . for 20 to 30 days . Patients were followed up for at least 1 year . Of the 14 ceftriaxone-treated patients four showed incomplete regression of the inflammatory skin changes after 6 to 12 months . Two out of five patients who were monitored for Borrelia burgdorferi DNA excretion were still positive after 12 months as compared to none of six patients who were treated orally for 20-30 days . Six out of 11 patients treated orally for only 20 days needed retreatment after 6 months because of continuing skin manifestations, neuropathy or arthralgia . A 30-day duration of treatment with oral antibiotics and not the chosen antibiotic is crucial for curing acrodermatitis chronica atrophicans . The duration of treatment with ceftriaxone needed for eradication of Borrelia in acrodermatitis chronica atrophicans has yet to be determined in future studies. Infection, 1996 Jan-Feb, 24(1), 80 - 4 Treatment of borrelial lymphocytoma; Strle F et al.; Treatment results in 65 patients with borrelial lymphocytoma (22 on the ear lobe and 43 on the breast), registered at the Department of Infectious Diseases, University Medical Centre Ljubljana, from January 1986 to March 1995, are presented . When lymphocytoma was the sole manifestation of Lyme borreliosis or associated with erythema migrans only patients were treated orally with doxycycline, phenoxymethylpenicillin or amoxicillin for 14 days, or azithromycin for 5 days (15, 19, six and 12 patients, respectively) . When signs and symptoms of disseminated borrelial infection were present (seven patients) or clinically suspected (six patients) patients received ceftriaxone or penicillin G i.v . for 14 days . Lymphocytoma disappeared within a few weeks after the institution of treatment . The speed of regression depended on the duration of lymphocytoma before the institution of therapy . The number of patients was too low and pretreatment characteristics were too heterogeneous to enable a reliable comparison of the efficacy of different antibiotics . It appears that the effectiveness of doxycycline and azithromycin is comparable and that amoxicillin performs well, but some findings may indicate that phenoxymethylpenicillin is less effective than some newer antibiotics . The optimal agent, dosage and duration of therapy for borrelial lymphocytoma have not been determined. Infection, 1996 Jan-Feb, 24(1), 69 - 72 Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis; Breier F et al.; An open, randomized, prospective study was carried out to compare the clinical efficacy and safety of phenoxymethylpenicillin with that of minocycline in the treatment of erythema migrans . Sixty patients (minocycline 30, penicillin 30) were enrolled in the study . The two groups of patients were statistically homogeneous regarding age and sex distribution . IgG and IgM antibodies against Borrelia burgdorferi were determined by ELISA before and after treatment and 1 year thereafter . Thirty-nine patients completed the study . All these patients (penicillin 21, minocycline 18) who received a 21-day course of treatment were free of clinical symptoms of late Lyme borreliosis after 1 year . Serum antibodies against B . burgdorferi could be detected before treatment in 6/21 patients treated with penicillin and 3/18 patients treated with minocycline . After 1 year 8/39 patients were seropositive without any evidence of ongoing disease . In the remaining 21 patients treatment could not be completed with the initial antibiotic due to side effects (penicillin 9/30, minocycline 12/30) . One patient, who stopped penicillin treatment at day 14 and one patient who stopped minocycline at day 4, developed fatigue and memory impairment within the observation period . A 3-week course of treatment with penicillin or minocycline is equally effective in treating patients with erythema migrans and preventing late symptoms of Lyme borreliosis. Chirality, 1996, 8(1), 67 - 76 Use of mathematically enhanced spectral analysis and spectral contrast techniques for the liquid chromatographic and capillary electrophoretic detection and identification of pharmaceutical compounds; Swartz ME et al.; The use of mathematically enhanced ultraviolet/visible (UV/VIS) absorbance spectral analysis and spectral contrast software techniques in high performance liquid chromatography (HPLC) and micellar electrokinetic capillary electrophoresis (MECC) as an aid for the determination of peak homogeneity, identification, and tracking during method development was investigated . Various structurally similar pharmaceutical compounds, and compounds present as either cis/trans isomers, diastereomers, or enantiomers were used as test compounds to probe the limits of this technique . Two tricyclic antidepressants, nortriptyline and imipramine, were employed to study the effects of HPLC mobile phase composition and pH on the ability to identify and track peaks during method development . It was found that method changes altered the spectral matches used for identification, but not enough to cause incorrect peak identification . It was also shown using HPLC that the cis/trans isomers of doxepin and the diastereomers ephedrine and pseudoephedrine could be distinguished . The mathematically enhanced spectral analysis and spectral contrast software techniques were also employed with MECC . Peaks tracking during method development as pH and the concentration of surfactant changes is shown for a separation of various penicillin type antibiotics . It was shown that during chiral MECC (CMECC) analyses ephedrine/pseudoephedrine diastereomers as well as ephedrine enantiomers could be distinguished . The determination of enantiomers is possible in CMECC since enantiomers are eluted as diastereomeric complexes, as opposed to HPLC where they are eluted in their native state. Sex Transm Dis, 1996 Jan-Feb, 23(1), 16 - 23 Epidemiology of syphilis in the United States, 1941--1993; Nakashima AK et al.; BACKGROUND AND OBJECTIVES . The distribution and trends of syphilis are influenced by biologic factors, sexual behaviors, biomedical technology, availability of and access to health care, public health efforts, changes in population dynamics, and sociocultural factors . The objective of this article is to review the epidemiology of syphilis in the United States during the period 1941-1993 in the context of some of these factors . STUDY DESIGN . Surveillance data on cases of syphilis and congenital syphilis reported by state and city health departments to the Centers for Disease Control and Prevention were analyzed to show distribution and trends by geographic location, racial and ethnic groups, gender, and age . RESULTS . Historically, syphilis was distributed widely throughout the country and declined rapidly after the introduction of penicillin therapy and broad-based public health programs, attaining its lowest levels in the 1950s . However, in recent years, the disease has returned and become focused in the southern region and in urban areas outside that region . Rates of syphilis have remained highest in black Americans, and the most recent national epidemic of syphilis primarily involved them . Rates in white men were at intermediate levels during the early 1980s but have declined to low rates in the 1990s, possibly because of changes in behavior in response to the AIDS epidemic . Rates in white women and other racial and ethnic groups have remained low throughout the 1980s and 1990s . CONCLUSIONS . Syphilis remains a significant problem in the United States, and its epidemiology is influenced by a complex combination of factors . To prevent and control syphilis effectively, public health practitioners must understand these factors and design programs and interventions that address the disease in the context of these factors. Acta Med Austriaca, 1996, 23(3), 99 - 101 Oral treatment of late Lyme borreliosis with a combination of roxithromycin and co-trimoxazole--a pilot study on 18 patients; Gasser R et al.; In this pilot trial, 18 patients participated in an investigation in which the combined therapy of co-trimoxazole and roxithromycin in late Lyme borreliosis was tested . The study has been performed as a result of earlier case reports in "The Lancet" where this combination has been used successfully in order to thwart late Lyme disease . The authors show that 76% of the patients recovered completely . In 2 patients, symptoms could be resolved with i.v . penicillin and 2 did not respond to any antibiotic therapy . These results show that oral therapy of co-trimoxazole and roxithromycin in combination provides similar results as i.v . antibiotics in earlier studies. Ukr Biokhim Zh, 1996 Jan-Feb, 68(1), 26 - 31 {Enzyme biosensors for penicillin determination based on conductometric planar electrodes and pH-sensitive field effect transistor}; Arkhipova VN et al.; The enzyme biosensors for penicillin determination based on conductometric planar electrodes and pH-sensitive field effect transistors have been described and their working parameters have been compared . The influence of pH, buffer capacity and ionic strength of the samples on the biosensors response has been studied . Short response time and high operational stability are characteristics of the developed biosensors. J R Coll Physicians Lond, 1996 Jan-Feb, 30(1), 37 - 41 The role of preventive medicine in sickle cell disease . The Watson Smith lecture; Serjeant GR; Homozygous sickle cell disease is one of the most common genetic abnormalities in the world; it affects approximately 100,000 births annually in Nigeria alone . With this scale of public health problem, the newer high technology approaches to prevention, such as antenatal diagnosis, or to treatment, such as bone marrow transplantation, are unlikely to be affordable or to have a discernible population impact . Experience in Jamaica suggests that many low technology affordable procedures can markedly reduce the morbidity and mortality of the disease . Furthermore, certain aspects of current management in the United Kingdom, such as frequent hospital admission and transfusion, not only consume scarce resources but may increase morbidity . Prophylactic penicillin to prevent pneumoccocal complications, education of parents so as to reduce the mortality from acute splenic sequestration, awareness of the features and epidemic pattern of aplastic crises, and exchange transfusion for the acute chest syndrome represent cost-effective measures which may markedly influence outcome . Reducing dependency on inpatient facilities might actually reduce morbidity and save resources that could be used to improve day care and outpatient management. Parasitol Res, 1996, 82(5), 475 - 6 Egg laying in vitro of Echinostoma caproni (Trematoda) in nutritive and nonnutritive media; Reddy A et al.; Egg laying in vitro was studied in Echinostoma caproni adults placed in 10 ml of nutritive or nonnutritive media for 48 h in petri-dish cultures maintained at 37 degrees C in an atmosphere containing 7.6% CO2 . Maximal egg laying occurred within 24 h in the defined medium RPMI 1640 . Egg laying was significantly greater in this medium than in McCoy's or Locke's solution . Eggs released into the RPMI medium were capable of producing miracidia that were infective to Biomphalaria glabrata snails . Fried and Huffman (1996) referred to a technique used to obtain eggs of Echinostoma caproni in the defined medium RPMI 1640, but details of the study were not given . No information is available on egg laying of echinostomes in vitro . Such information could contribute to a better understanding of egg release in digeneans and would also be helpful in the acquisition of eggs for biology and chemistry studies . Current techniques used to obtain echinostome eggs involve worm homogenization, teasing of eggs from the worms' uteri, or recovery of eggs from feces (see Idris and Fried 1996 for details) . The purpose of this communication is to report on an efficient procedure for the acquisition of eggs of E . caproni after the placement of adult worms in the defined medium RPMI 1640 . E . caproni adults were grown in ICR mice for either 17 (young worms) or 112 days (old worms) as described previously (Ursone and Fried 1995a) . Worms were removed from the small intestines and rinsed rapidly in three changes of sterile Locke's solution containing penicillin (200 IU/ml) and streptomycin (200 micrograms/ml; Fried and Contos 1973) . Worms were placed in culture media within 30 min of their removal from hosts . Nutritive media consisted of RPMI 1640 and McCoy's medium (Sigma, St . Louis, Mo.) . Non-nutritive media consisted of Locke's or Locke's 1:1 (Ursone and Fried 1995b) . All media contained antibiotics as described above. Vet Res, 1996, 27(2), 147 - 59 Pharmacokinetics of penicillin G in plasma and interstitial fluid collected with dialysis fiber bundles in sheep; Cooke IM et al.; A new method of collection of interstitial fluid (ISF) (the site of most bacterial infections) was developed for the determination of free (unbound) penicillin G concentrations in sheep . Dialysis fiber bundles for the collection of ISF were first characterized in vitro and subsequently implanted in the subcutaneous fascia of the dorsal thorax parallel to the vertebral column in sheep . The sheep were then dosed intravenously with 26.4 and 52.9 mg/kg of sodium penicillin G using a crossover experimental design . Plasma and ISF dialysate were collected after dosing for determination of penicillin G concentrations using high pressure liquid chromatography (HPLC) . The concentration of penicillin G in the ISF dialysate was calculated with the recovery ratio determined for each fiber bundle . The decline of penicillin G concentrations in ISF dialysate paralleled the disappearance of the drug from plasma providing evidence for the rapid diffusion of penicillin G into the fiber bundles . Pharmacokinetic analysis determined that the disposition of penicillin G was best described by a two-compartment open model with penicillin concentrations in plasma (Cp) defined by two biexponential equations, Cp = 170.64e-7.16t + 31.04e-1.56t for the low dose and Cp = 418.19e-1.56t for the high dose. Clin Electroencephalogr, 1996 Jan, 27(1), 22 - 5 Dyshormia revisited: generalized seizures and arousal; Nowack WJ; Niedermeyer has described dyshormia, or deviant arousal, and related this EEG pattern to generalized seizures . We describe a patient with generalized seizures who in the same EEG had spindles transforming into generalized epileptiform discharges and generalized epileptiform discharges transforming into spindles . This suggests that similar neural circuitry may underlie both spindles and generalized epileptiform discharges, and that the mechanism described by Gloor for feline generalized penicillin induced epilepsy may also apply to some humans with generalized epilepsies. Appl Microbiol Biotechnol, 1996 Jan, 44(5), 597 - 604 Mutants blocked in penicillin biosynthesis show a deletion of the entire penicillin gene cluster at a specific site within a conserved hexanucleotide sequence; Fierro F et al.; The organization of the genes of the penicillin cluster has been studied in three different mutants of P . chrysogenum impaired in penicillin biosynthesis . The three blocked mutants (derived from the parental strain P . chrysogenum Bb-1) lacked the genes pcbAB, pcbC and penDE of the penicillin biosynthetic pathway and were unable to form isopenicillin N synthase and isopenicillin N acyltransferase . All strains were identified as P . chrysogenum derivatives by fingerprinting analysis with (GTG)n as a probe . The borders of the deleted region were cloned and sequenced, showing the same junction point in the three mutants . The deleted DNA region was found to be identical to that described in P . chrysogenum npe10 . The frequent deletion of the pen gene cluster at this point may indicate that this cluster is located in an unstable genetic region, flanked by hot spots of recombination, that is easily lost by mutagen-induced recombination. J Formos Med Assoc, 1996 Jan, 95(1), 66 - 8 Gastric actinomycosis; Lee CM et al.; A case of actinomycosis of the stomach in a 61-year-old woman is reported . The patient presented to the hospital with a history of epigastric pain, fatigue, poor appetite, constipation and mild fever of 20 days' duration . On physical examination, a tender mass was felt at the epigastrium . Computed tomography (CT) showed a heterogeneously enhanced mass at the posterior wall of the stomach . Upper gastrointestinal series revealed a submucosal mass at the gastric antrum . A malignant tumor was suspected and surgery was recommended . A 5 x 4 x 2 cm mass was found at the posterior wall of the distal gastric antrum . A Billroth II subtotal gastrectomy was performed . Pathologic examination revealed suppuration and sulfur granules in the indurated mass . The patient was subsequently treated with intravenous penicillin-V for 12 days and then with oral penicillin-G for 4 months . She remained well at her last follow-up appointment . Although the initial radiologic findings were nonspecific, CT was of importance in delineating the location and evaluating the extent of the lesion. Mol Immunol, 1996 Jan, 33(1), 71 - 7 Interleukin-4 plays a dominant role in Th1- or Th2-like responses during the primary immune response to the hapten penicillin; Kerdine S et al.; Despite a large number of studies on the Thl/Th2 balance during immune response to pathogens or protein antigens, little is known concerning the early events which regulate Thl/Th2 differentiation following a single injection of haptenic compounds . In this work, we studied how two mouse strains with different MHC haplotypes, SJL (H-2s) and Balb/c (H-2d), could develop different primary immune responses to subcutaneously injected benzylpenicillin coupled to tetanus toxoid (BPO-TT) . The SJL mice showed a high BPO-specific IgG1 response that was maximum on day 10 and no BPO-specific IgG2a response . In contrast, Balb/c mice showed a high BPO-specific IgG2a response on days 15 and 22 and a weak IgG1 production . In SJL mice, the response to BPO-TT was characterized by a very early and high IL-4 mRNA expression . In Balb/c, a delayed and weaker expression of IL-4 mRNA was observed . Kinetics of IL-2 and IFN-gamma mRNA expression were comparable in both strains, but IFN-gamma mRNA expression was higher in SJL than in Balb/c . In vivo neutralization of IL-4 induced a significant BPO-specific IgG2a production and a two-fold reduction of IgG1 production in SJL mice while it accelerated production of BPO-specific IgG2a in Balb/c mice . In addition, studies of IL-12 p4O and IL-10 mRNA expression following immunization with BPO-TT showed a greater IL-12 p4O mRNA expression in Balb/c mice and a slightly higher IL-10 mRNA expression in SJL . Taken together, our data suggest that Th1 or Th2 differentiation in primary immune responses to haptenic compounds such as penicillin may be driven by the kinetics and the level of IL-4 production rather than by the level of IFN-gamma . Additional cytokines such as IL-10 and IL-12 are likely to contribute to the regulation of this response. Dis Colon Rectum, 1996 Jan, 39(1), 105 - 8 Abdominal actinomycosis; Cintron JR et al.; PURPOSE: Actinomyces israelii are normal inhabitants in the oral cavity and upper intestinal tract of humans . They rarely cause disease and are seldom reported as pathogens . As a pathogen it causes fistulas, sinuses, and may appear as an abdominal mass and/or abscess . The abdominal mass can masquerade as a malignant process that is very difficult to differentiate, often requiring surgical intervention with resection . Because of difficulty in making a preoperative diagnosis, we undertook this review to determine if all patients require surgical intervention and whether other adjunctive modalities may improve preoperative diagnosis . METHODS: We report two patients with abdominal actinomycosis, one affecting the sigmoid colon and the other the retroperitoneum, iliac crest region . Both simulated a malignant process and required operations for diagnosis and treatment . RESULTS: As reported, actinomycotic abdominal masses and strictures can be treated by penicillin alone . Long-term medical treatment seems to be very successful and avoids surgical resection . The difficulty is obtaining a definitive diagnosis . CONCLUSION: The computed tomographic scan is the most helpful diagnostic modality . Appearance of abdominal actinomycosis is usually a contrast enhancing multicystic lesion as was found in these two patients . Needle aspiration cytology can be fairly accurate in obtaining the diagnosis and is recommended for suspicious lesions. J Invest Dermatol, 1996 Jan, 106(1), 176 - 82 Modeling acne in vitro; Guy R et al.; To help elucidate the factors responsible for the infundibular changes seen in acne, the human sebaceous pilosebaceous infundibulum was isolated by microdissection and maintained for 7 d in keratinocyte serum-free medium supplemented with 50 micrograms/ml bovine pituitary extract, 100 units/ml penicillin and streptomycin, 2.5 micrograms/ml amphotericin B and CaCl2(10H2O) to give a final Ca2+ concentration of 2 mM . Infundibular structure was maintained over 7 d in this medium; the pattern of cell division mimicked that in vivo . The rate of cell division was significantly higher than previously described for infundibula maintained in supplemented William's E medium, and moreover did not fall over 7 d . The addition of 1 ng/ml interleukin-1 alpha (IL-1 alpha) caused hypercornification of the infundibulum similar to that seen in comedones; this could be blocked by 1000 ng/ml interleukin-1 receptor antagonist (IL-1ra) . In about 20% of subjects there was spontaneous hypercornification of the infundibulum that could be blocked by 1000 ng/ml IL-1ra, suggesting that the infundibulum is capable of synthesising IL-1 alpha . The addition of 5 ng/ml epidermal growth factor or 5 ng/ml transforming growth factor-alpha to the medium caused a disorganisation of the keratinocytes of the infundibulum that resulted in rupturing similar to that seen in the more severe, purulent grades of acne . The addition of 1 microM 13-cis retinoic acid caused a significant reduction in the rate of DNA synthesis and apparent parakeratosis . We are now, therefore, able to model histologically the major infundibular changes in acne. Eur J Immunol, 1996 Jan, 26(1), 42 - 8 T cell recognition of penicillin G: structural features determining antigenic specificity; Padovan E et al.; Penicillin G (Pen G) and other beta-lactam antibiotics frequently induce allergic reactions constituting typical examples of human immune responses to haptens . In fact, penicillins represent a unique set of haptens with outstanding structural variability on the basis of an identical protein-reactive beta-lactam containing backbone . Although both cellular and humoral responses are involved in drug-induced allergies, little is known about the T cell reactivity to penicillins . To understand which structural features determine antigenic specificity, we isolated a panel of MHC-restricted, Pen G-reactive T cell clones from different penicillin-allergic patients and tested them for their capacity to proliferate in the presence of other penicillin derivatives . We found that the antigenic epitope consists of both the amide-linked side chain, which is different in every member of the penicillin family, as well as the thiazolidine ring common to all penicillin derivatives . We also demonstrated the presence of two different types of penicillin-specific T cells, one dependent, and the other independent of antigen processing by autologous antigen-presenting cells . Our data strongly suggest that penicillins form part of the epitopes contacting the antigen receptors of T cells. Dig Dis Sci, 1996 Jan, 41(1), 180 - 4 Nafcillin-associated hepatotoxicity . Report of a case and review of the literature; Presti ME et al.; Nafcillin is a semisynthetic penicillin that is generally well tolerated with few side effects . Hepatic complications are rare but have a potential for serious liver dysfunction . This unusual complication causes a predominantly cholestatic injury, which can persist for prolonged periods even after discontinuing the medication . The pathophysiology may include direct cytotoxicity or an immune-mediate hypersensitivity . Treatment is generally supportive, except for severely symptomatic patients who may require steroids . We report a case of nafcillin-associated hepatotoxicity and review the literature of this disorder. BMJ, 1995 Dec 16, 311(7020), 1600 - 2 Improved survival in homozygous sickle cell disease: lessons from a cohort study; Lee A et al.; OBJECTIVE: To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease . DESIGN: Survival curve analysis and hazard ratios in a cohort study followed from birth . SETTING: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica . SUBJECTS: 315 patients with homozygous sickle cell disease detected during the screening of 100,000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica . INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic . MAIN OUTCOME MEASURES: Survival . RESULTS: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P = 0.05) . Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P = 0.02) . CONCLUSION: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease. Bone Marrow Transplant, 1995 Dec, 16(6), 743 - 6 Allogeneic bone marrow transplantation for primary myelofibrosis; Singhal S et al.; The published experience of allogeneic bone marrow transplantation for primary myelofibrosis (PMF) is limited . Three patients (24-49 years) with PMF received allogeneic marrow grafts from HLA-identical sibling donors after conditioning with 110 mg/m2 melphalan and 1050 cGy total-body irradiation (TBI) . Donor marrow was not depleted of T cells, and graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine and methotrexate . None of the patients was splenectomized prior to the transplant . Two patients received G-CSF post-transplant to hasten neutrophil recovery . One patient died of multi-organ failure 23 days post-transplant . Hematopoietic recovery was relatively slow in the other two who had gradual resolution of the marrow fibrosis over several months . One of the two died of overwhelming pneumococcal sepsis within 2 weeks of stopping prophylactic penicillin 31 months post-transplant . The other patient is alive and well 20 months post-transplant with a Karnofsky score of 100% and no fibrosis of the marrow . We conclude that PMF is correctable by allogeneic BMT . Hematologic recovery post-transplant is slow, but counts may normalize with time without the need for splenectomy. Obstet Gynecol Surv, 1995 Dec, 50(12), 845 - 50 Lues-lues: maternal and fetal considerations of syphilis; Ray JG; Although syphilis occurs infrequently among Canadian and American women, global antenatal screening is still warranted . The reason is that congenitally acquired syphilis is serious, yet largely preventable . Those women at highest risk for the disease seem to be crack and cocaine users, as well as those without antenatal care . These women should be screened for syphilis during the first and early-third trimesters, whenever possible, or at the time of delivery . HIV testing should be routinely recommended . Syphilis is diagnosed using microscopy and/or serologic testing . Although nontreponemal serology (VDRL and RPR) is acceptable as the initial screening test, sensitivity and specificity for syphilis vary between 60 and 75 percent and 84 and 99 percent, respectively . These are also many causes of false-positive test results . Treponemal serology (FTA-ABS and MHA-TP) are used to confirm nontreponemal tests . The only acceptable treatment of syphilis during pregnancy is penicillin . For those with disease of less than 1 year's duration, it is suggested that two doses of benzathine penicillin G (2.4 million units I.M.) be administered 1 week apart . Disease of greater or unknown duration requires a longer, modified regimen . Serious adverse reactions to therapy are rare, and penicillin-allergic mothers can be skin tested, followed by desensitization if required . Exactly how HIV infection modifies the detection and treatment of syphilis in pregnancy is unclear . Treatment of HIV-infected women with syphilis is presently no different than non-HIV patients, unless invasion of the central nervous system is suspected. West J Med, 1995 Dec, 163(6), 552 - 9 Syphilis . A tale of twisted treponemes; Flores JL; Despite the widespread availability of effective treatment, the incidence of primary and secondary syphilis in the United States is on the rise . In addition, syphilis is occurring in a substantial number of patients infected with the human immunodeficiency virus (HIV), thus adding to the complexities of diagnosis and treatment . Primary syphilis represents a disseminated infection, often accompanied by abnormalities of the cerebrospinal fluid, that may pass unrecognized and progress to the myriad manifestations of secondary syphilis . The diagnosis of syphilis in patients with mucosal or skin lesions may be made by darkfield examination; once lesions have resolved, serologic tests are required . Patients with latent syphilis may have asymptomatic neurosyphilis and risk progression to tertiary disease . The diagnosis of asymptomatic neurosyphilis is necessary to determine the optimal treatment of patients with latent disease . The diagnosis of active neurosyphilis generally requires an inflammatory cerebrospinal fluid profile and a reactive cerebrospinal fluid VDRL test . Syphilis is common in HIV-infected patients, who may have an altered antibody response to infection and an apparent increased incidence of neurologic complications . The preferred treatment at all stages is penicillin, which is also the only recommended therapy for neurosyphilis . The optimal treatment of syphilis in HIV-infected patients is unknown. No To Shinkei, 1995 Dec, 47(12), 1143 - 8 {Experimental study on hypertensive crises in epileptic seizures--changes in pial artery diameter, intracranial pressure and regional cerebral blood flow}; Eguchi T et al.; It is well known that severe hypertension occurs during epileptic seizures, but little information is available concerning these hypertensive crises . We therefore investigated them by monitoring regional cerebral blood flow (rCBF), intracranial pressure (ICP) and pial artery diameter (PAD) in paralyzed mechanically-ventilated cats with penicillin-induced seizures . The animals were assigned to two groups . In one (Group H), they were maintained in an untreated state . In the other (Group C), spinal cord injury was performed in advance to prevent the rise in arterial blood pressure during the seizures . In both groups, the values of the various parameters increased during seizure activity, but the increases in group H, were greater than in group C . In both groups, PAD, rCBF and ICP increased immediately at the onset of the seizures with no hypertension . In group H, further increases in PAD, rCBF, and ICP were found concurrent with the elevation of arterial blood pressure in the latter half of the seizure, while in group C, rCBF decreased concurrent with the increase in ICP in the latter half of the seizure, although PAD was found to be maximal . These findings suggest that hypertensive crises during epileptic seizures represent a protective mechanism to maintain perfusion pressure. Chest, 1995 Dec, 108(6), 1608 - 13 Bacteremic pneumococcal pneumonia . A community hospital experience; Lippmann ML et al.; We reviewed our experience with bacteremic pneumococcal pneumonia (BPP) over a 1-year period at a 600-bed community teaching hospital; 26 cases were identified . The mean age was 57.5 years and there were 12 male and 14 female subjects . Cough, sputum production, fever, and mental status changes were the most frequent symptoms . Risk factors included drug abuse in 10, HIV in 4, current smoking in 7, diabetes in 3, and cancer in 3 . The mean PaO2/FIo2 ratio was 274 . Radiographic features included a consolidation pattern in 7, bronchopneumonia in 15, combined in 1, and an initial normal film in 3 . Average length of stay (LOS) was 11 days with an overall mortality of 11.5% . Four patients required mechanical ventilation, two meeting the criteria for ARDS (if this group were eliminated, LOS would be 8.4 days) . Three of these survived . Four patients had organisms resistant to penicillin and all survived . We conclude that (1) BPP remains a serious but treatable infection particularly when utilizing full supportive care; (2) the bronchopneumonia x-ray film pattern was associated with all the mortality; and (3) the occurrence of penicillin resistance did not contribute to the mortality, since early recognition and the use of appropriate antibiotics saved all of these patients. J Mol Biol, 1995 Nov 24, 254(2), 223 - 36 The refined crystallographic structure of a DD-peptidase penicillin-target enzyme at 1.6 A resolution; Kelly JA et al.; The D-alanyl-D-alanine peptidase from Streptomyces sp . R61 is a 37,500 dalton exocellular enzyme that has served as a model for membrane-bound peptidases that are involved in bacterial cell wall biosynthesis . Inhibition of these enzymes by beta-lactam antibiotics ultimately leads to bacterial cell death . The X-ray crystal structure of the R61 D-alanyl-D-alanine peptidase has been solved using multiple isomorphous replacement, simulated annealing and least squares refinement . The space group and unit cell parameters are P2(1)2(1)2(1) with a = 51.1 A, b = 67.3 A and c = 102.4 A . The structure has been refined using 2 sigma data to 1.6 A resolution with a crystallographic R-factor of 0.148 . The model contains 347 residues (2938 atoms) and 254 solvent molecules . The overall temperature factor is 9.6 A2, and the estimated coordinate error is 0.14 A . The protein consists of a single polypeptide chain organized into two regions . One region contains a nine-stranded antiparallel beta-sheet with helices on both faces; this region includes both the amino and carboxyl termini . The second region is all helical . Sixty percent of the residues occur in helices or beta-sheet . The reactive Ser62 is found between the two regions of the enzyme at the amino end of the protein's longest-helix which begins with one turn of 3(10) helix and continues with four turns of alpha-helix . The active site is an elongated pocket that contains four basic and four aromatic residues . An oxyanion hole is formed by Ser62 NH and Thr301 NH . The pocket also contains the few key residues that are conserved in all penicillin-binding proteins and beta-lactamases . Two of these residues, Lys65 and Tyr159, are among the 16 side-chains that take on multiple conformations in the R61 crystal structure . Three of the 12 proline rings adopt two conformations which we believe has not been previously reported . There is no anionic acid equivalent to the catalytic Glu166 found in Class A beta-lactamases . Two ordered water molecules (O507 and O644) are found buried in the active site and hydrogen-bonded to each other (2.6 A) . O507 could potentially act as the hydrolytic water molecule for deacylation. Nature, 1995 Nov 23, 378(6555), 416 - 9 A protein catalytic framework with an N-terminal nucleophile is capable of self-activation; Brannigan JA et al.; The crystal structures of three amidohydrolases have been determined recently: glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome . These enzymes use the side chain of the amino-terminal residue, incorporated in a beta-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon . The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome . Here we show that all three enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites . This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing . We suggest the name Ntn (N-terminal nucleophile) hydrolases for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recognizable sequence similarity. Mol Gen Genet, 1995 Nov 15, 249(2), 237 - 45 Secretion of active beta-lactamase to the medium mediated by the Escherichia coli haemolysin transport pathway; Chervaux C et al.; An in frame gene fusion containing the coding region for mature beta-lactamase and the 3'-end of hylA encoding the haemolysin secretion signal, was constructed under the control of a lac promoter . The resulting 53 kDa hybrid protein was specifically secreted to the external medium in the presence of the haemolysin translocator proteins, HlyB and HlyD . The specific activity of the beta-lactamase portion of the secreted protein (measured by the hydrolysis of penicillin G), approximately 1 U/microgram protein, was close to that of authentic, purified TEM-beta-lactamase . This is an important example of a hybrid protein that is enzymatically active, and secreted via the haemolysin pathway . Previous studies have indicated that haemolysin is secreted directly into the medium, bypassing the periplasm, to which beta-lactamase is normally targeted . This study indicated, therefore, that normal folding of an active beta-lactamase, can occur, at least when fused to the HlyA C-terminus, without the necessity of entering the periplasm . Despite the secretion of approximately 5 micrograms/ml levels of the active beta-lactamase fusion into the medium, there was maximally only a 50% detectable increase in the LD50 for resistance to ampicillin at the individual cell level . This result suggests that, normally, resistance to ampicillin requires a high concentration of the enzyme close to killing targets, i.e . in the periplasm, in order to achieve significant levels of protection. Lancet, 1995 Nov 11, 346(8985), 1242 - 3 Pneumocystis carinii in Africa: an emerging pathogen? Russian DA, Kovacs JA. PIP: There are quite a few pathogens which can cause pneumonia . Identifying the agent of infection simplifies therapy by allowing the appropriate treatment to be targeted with a minimum amount of toxic drugs . Empirical therapy is ideally reserved for settings in which the patient is not acutely ill, there is a high probability of a single, easily treated pathogen, and rapid diagnostic facilities are available if treatment fails . Empirical therapy, however, is often necessary in many AIDS-endemic regions where diagnostic tests are unavailable due to limited resources . In such circumstances, a treatment algorithm independent of extensive diagnostic testing and targeted against locally prevalent pathogens is called for . Malin and colleagues have reported finding Pneumocystis carinii pneumonia (PCP) among 33% of 64 patients in Zimbabwe observed with diffuse pneumonia unresponsive to penicillin . Untreated PCP is lethal . Further, despite three negative sputum smears for Mycobacterium tuberculosis, the organism was the most common pathogen ultimately identified, confirming previous reports and highlighting the importance of anti-TB therapy . The high incidence of PCP raises concerns that in certain parts of Africa treatment algorithms which do not consider PCP may need to be re-evaluated . Different patient selection criteria among studies with discordant results may partially explain the differences in the incidence of PCP in different parts of Africa . Otherwise, regional environmental differences, host genetic variation, and differences in the virulence of various strains of P . carinii may play a role . Data on the incidence of PCP in HIV-infected infants in Africa would provide insights into the role of P . carinii as a pathogen . The authors note that if the incidence of PCP is rising, even in selected areas, then prophylaxis in such areas with co-trimoxazole may be a cost-effective management approach which may also decrease the incidence of bacterial infections . Alternatively, early empirical therapy with co-trimoxazole at high doses may be an effective approach for treating both PCP and bacterial infections before the initiation of empirical anti-TB therapy . J Membr Biol, 1995 Nov, 148(2), 193 - 202 Rapid desensitization of alpha 1 beta 1 GABA A receptors expressed in Sf9 cells under optimized conditions; Birnir B et al.; alpha 1 and beta 1 subunits of human GABA A receptors were expressed in Sf9 cells using the Sf9-baculovirus system . Better expression was obtained by manipulating the system . Cell growth phase at the time of infection determined the practical range of virus titre, the period postinfection during which cells were useful for signal detection and the maximal current obtained . Cells in the early exponential phase were relatively insensitive to multiplicity of infection (MOI) whereas cells in the mid- to late-exponential phase were highly dependent on MOI and they responded with the largest Cl- current generated by GABA . Channels activated by GABA were chloride-selective . Half the maximum peak whole-cell current was obtained with 11 microM GABA . The time course of Cl- currents activated by saturating GABA concentrations in cells infected with alpha 1 beta 1-recombinant viruses was examined employing a rapid perfusion system which allowed whole-cell solution exchange in less than 1 msec . The current decay could be fitted by 3 to 4 exponentials for the first 8 sec . The initial fast current decrease had a time constant of about 23 msec . No voltage dependence of time constants was detected but the whole-cell IV relation showed outward rectification . Currents were depressed by bicuculline, penicillin and picrotoxin and potentiated by pentobarbitone. Clin Neurol Neurosurg, 1995 Nov, 97(4), 285 - 9 The perioperative use of ceftriaxone as infection prophylaxis in neurosurgery; Zhao JZ et al.; An open label study was conducted in the department of neurosurgery, Beijing Tiantan Hospital in China to determine the incidence of postoperative infections following the use of one or two doses of ceftriaxone administered perioperatively . A total of 343 patients, who required neurosurgery and had satisfied the inclusion criteria, was recruited during a 12 month study period . Of these 343 patients, there were 97 and 107 cases of malignant and benign tumours, respectively, 52 cases of aneurysm, 34 cases of arteriovenous malformation, and 53 other cases who underwent neurosurgery for drainage of sub-dural haematoma, relief of cerebral oedema and other indications . A total of 6 (1.75%) cases of postoperative infection was observed, of which 4 were found in the malignant tumour group, and 2 in the arteriovenous malformation group . All six patients were suffering from meningitis . During the 12 month period immediately prior to the present study, when postoperative penicillin and gentamicin was administered twice daily for 5-7 days as regular prophylaxis against infection, the incidence of postoperative infection was 7.2% in the same department managed by the same staff . Results of our present study suggest that one to two doses of ceftriaxone administered perioperatively are effective in reducing the rate of postoperative infections. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1995 Nov-Dec, 36(6), 445 - 7 Mesenteric arterial thrombosis complicating congenital nephrotic syndrome of Finnish type: report of one case; Tsai MJ et al.; A female, term neonate presented with generalized edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia in the second week of life . The clinical and laboratory features were compatible with the diagnosis of congenital nephrotic syndrome . Treatment included albumin infusion, empirical penicillin, steroid and continuous arterio-venous hemofiltration . Intestinal perforation developed at the 19th day of age and led to a fatal outcome . At autopsy, thrombosis of the superior mesenteric artery and its branches was noted, and histology of the kidney was compatible with congenital nephrotic syndrome of the Finnish type . The risk of thromboembolism, arterial or venous, should be considered in patients with nephrotic syndrome, even in the neonatal period . Preventive measures, including avoiding volume depletion and femoral arterial/venous puncture, are essential in managing these patients . Prophylactic anticoagulation and infusion of fresh frozen plasma may be warranted to avoid such potentially lethal complications of thromboembolism. J Bacteriol, 1995 Nov, 177(21), 6290 - 3 Hybrid proteins of the transglycosylase and the transpeptidase domains of PBP1B and PBP3 of Escherichia coli; Zijderveld CA et al.; The construction of hybrid proteins of PBP1B and PBP3 has been described . One hybrid protein (PBP1B/3) contained the transglycosylase domain of PBP1B and the transpeptidase domain of PBP3 . In the other hybrid protein, the putative transglycosylase domain of PBP3 was coupled to the transpeptidase domain of PBP1B (PBP3/1B) . The hybrid proteins were localized in the cell envelope in a similar way as the wild-type PBP1B . In vitro isolates of the strains containing the hybrid proteins had a transglycosylase activity intermediate between that of wild-type PBP1B-producing strain and that of a PBP1B overproducer . Analysis with specific antibiotics against PBP1A/1B and PBP3 and mutant analysis in strains containing PBP3/1B revealed no detectable effects in vivo compared with wild-type strains . The same was shown for PBP1B/3 when the experiments were performed in a recA background . The data indicate that the hybrid proteins cannot replace native penicillin-binding proteins . This finding suggests that functional high-molecular-weight penicillin-binding protein specificity is at least in part determined by the unique combination of the two functional domains. J Bacteriol, 1995 Nov, 177(21), 6069 - 76 A lacZ reporter fusion method for the genetic analysis of regulatory mutations in pathways of fungal secondary metabolism and its application to the Aspergillus nidulans penicillin pathway; Perez-Esteban B et al.; Secondary metabolism, usually superfluous under laboratory conditions, is intrinsically elusive to genetic analysis of its regulation . We describe here a method of analyzing regulatory mutations affecting expression of secondary metabolic genes, with an Aspergillus nidulans penicillin structural gene (ipnA {encoding isopenicillin N-synthase}) as a model . The method is based on a targeted double integration of a lacZ fusion reporter gene in a chromosome different from that containing the penicillin gene cluster . The trans-acting regulatory mutations simultaneously affect lacZ expression and penicillin biosynthesis . One of these mutations (npeE1) has been analyzed in detail . This mutation is recessive, prevents penicillin production and ipnA'::'lacZ expression, and results in very low levels of the ipnA message at certain times of growth . This indicates that npeE positively controls ipnA transcription . We also show that this tandem reporter fusion allows genetic analysis of npeE1 by using the sexual and parasexual cycles and that lacZ expression is an easily scorable phenotype . Haploidization analysis established that npeE is located in chromosome IV, but npeE1 does not show meiotic linkage to a number of known chromosome IV markers . This method might be of general applicability to genetic analysis of regulation of other fungal secondary metabolic pathways. Clin Chem, 1995 Nov, 41(11), 1654 - 61 Calcium ion binding to clinically relevant chemical modifications of human serum albumin; Vorum H et al.; Calcium binding to glycated, penicilloylated, acetylated, and normal defatted human serum albumin as well as to mercapt- and nonmercaptalbumin was studied by equilibrium dialysis of radioactive Ca2+ . Binding was quantified by five Scatchard constants {ni = 1, (i = 1-4) and n5 = 10} . Glycation resulted in increased k1- and k2-values and unchanged k3-k5-values, whereas penicilloylation increased all five association constants . The increments were greater the more pronounced the modification, and the enhancements caused by penicilloylation were, for the same degree of modification, greater than those produced by glycation . In contrast, acetylation by acetylsalicylate did not affect calcium binding . Likewise, binding to mercapt- and nonmercaptalbumin was the same, a finding showing that the thiol group of cysteine 34 is not important for calcium binding . D-Glucose and penicillin G are known to react with lysine residues of albumin, and the enhancement of binding resulting from glycation or penicilloylation is probably brought about by unspecific electrostatic effects, possibly supplemented by conformational changes of the protein molecule . The relative importance of the three domains of human serum albumin for calcium binding is discussed. Ann Emerg Med, 1995 Nov, 26(5), 621 - 31; discussion 632-4 Ventricular fibrillation, automatic external defibrillators, and the United States Food and Drug Administration: confrontation without comprehension; Cummins RO et al.; More people die in the United States each day of potentially reversible VF than of any other cause of death, reversible or not . Early defibrillation is the definitive treatment . Automated external defibrillation is a proven technology now confirmed to have saved thousands of lives . As with all medical devices and technology, perfection is not possible . Some problems, such as those represented by the two cases discussed in this article, are inevitable and acceptable and give little cause for alarm . One would not stop penicillin from being manufactured and distributed because of a sudden, unexpected allergic reaction in one patient (error of commission) or an unexpected resistant organism in another (error of omission) . The FDA must understand that AEDs, even if they are imperfect, are not anywhere near as dangerous as no defibrillator at all . AEDs have finally allowed many EMS systems to achieve early defibrillation . Discontinuing use of AEDs or closing AED manufacturers could mean a significant number of lives lost unnecessarily . Therefore EMS agencies planning to implement early-defibrillation programs should continue with such plans . Why the agents of an important federal regulatory agency have singled out this technology for an intense review puzzles many observers in the medical-device field . Two meetings have been hosted by officials of the FDA to discuss the continuing concern the FDA officials have expressed over automated defibrillation technology . These meetings included representatives from the AHA, the American College of Cardiology, ACEP, defibrillator manufacturers, and other interested organizations . The FDA leadership has repeatedly focused on data acquired through the FDA Medical Device Reporting systems . Congress requires the FDA to investigate reports of problems with "critical medical devices." Because the indication for the use of a defibrillator is cardiac arrest, there will inevitably be a high association between defibrillator use and patient deaths . FDA personnel may view such reports of device problems in association with patient deaths as evidence that an intrinsically flawed technology has reached the marketplace without rigorous testing and evaluation . From the clinician's perspective, however, these reports represent a small numerator over a huge denominator of daily, lifesaving clinical use . The non-FDA participants at the two meetings have stated that the FDA complaints appear to be random and reveal a lack of understanding of AED technology.(ABSTRACT TRUNCATED AT 400 WORDS) Epilepsy Res, 1995 Oct, 22(2), 97 - 106 Mechanism of valproic acid uptake by isolated rat brain microvessels; Naora K et al.; In an effort to characterize putative transport systems of valproic acid (VPA) at the blood-brain barrier, the effects of various substrates and inhibitors of known anion transporters on the equilibrium vessel-to-medium concentration (vessel/medium) ratio of VPA were investigated using isolated rat brain microvessels . The equilibrium vessel/medium ratio of VPA was decreased by the presence of high millimolar concentration of unlabeled VPA, indicating that a saturable transport system was involved in VPA transport from medium to microvessels . Short-chain monocarboxylates such as propionic acid, pyruvic acid, and L-lactic acid did not alter the vessel/medium ratio, whereas medium-chain fatty acids and unsaturated metabolites of VPA significantly inhibited the net transport of VPA . Dicarboxylates, tricarboxylate, and p-aminohippuric acid did not affect VPA accumulation in the brain microvessels . Several anionic drugs including salicylic acid, penicillin G, cefazolin, and probenecid significantly reduced the vessel/medium ratio of VPA . In addition, disulfonate inhibitors of inorganic anion exchangers, SH-group modifying reagent, and metabolic inhibitor showed remarkable inhibitory effects on the net transport of VPA between brain microvessels and medium . These results suggest that VPA may be actively transported through the antiluminal membrane via a carrier-mediated system shared by other anionic drugs. Epilepsy Res, 1995 Oct, 22(2), 127 - 36 Repeated penicillin-induced amygdala epileptic focus in freely moving cats . EEG, polysomnographic (23-h recording), and brain mapping study; Fernandez-Guardiola A et al.; The effect of repeated Na-penicillin (PCN) microinjections in the temporal lobe amygdala (AM) of free-moving cats was investigated in order to establish if kindling epileptogenesis is possible with this procedure . The cortical propagation of the PCN-induced post-discharge in AM and the sequence of behavioral changes induced by PCN were similar to those of AM electrical kindling . Nevertheless, the epileptogenic effect of PCN had a different evolution from that of electrical kindling, since some PCN habituation was observed after several doses . Repeated microinjections of PCN did not produce lasting alterations in sleep onset and organization . The only mild changes recorded in the 23 h following PCN microinjections were an increased latency of the first rapid eye movement (REM) sleep episode, a SWS II total time and percentage increase, and, with the highest PCN doses, a not very significant diminution of REM sleep total time . Another finding was the occurrence of REM sleep ponto-geniculo-occipital (PGO) waves, coinciding with a depression of the frequency and amplitude of interictal amygdaloid and cortical spikes . The results showed that a microinjection of PCN in the AM produced a reliable model of interictal spikes, paroxysms and generalized convulsive seizures . Nevertheless, long lasting kindling effect was not observed. Ethiop Med J, 1995 Oct, 33(4), 251 - 7 Rupture of pregnant uterus in Shashemene General Hospital, south Shoa, Ethiopia (a three year study of 57 cases); Chamiso B; This study was carried out to determine the frequency of occurrence and outcome of treatment of uterine rupture in a rural hospital . Fifty seven patients with uterine rupture were admitted to Shashemene General Hospital (SGH) from September 1989 to August 1992 . The age, parity, type of operation, outcome of treatment, site of rupture, post operative complications and duration of hospitalization of these cases were analyzed . Two thousand one hundred eighty five deliveries were conducted over the study period . The frequency of occurrence of uterine rupture was 2.6% or 1 in 38 deliveries . There were 9 deaths giving a case fatality rate of 15.8% . The mean duration of hospitalization among those who survived was 13 days (Range: 6 hours to 20 days) . Fifty four (94.7%) of the cases were para 3 and above . Left lateral wall rupture was found in 28 (49%) of the cases . The commonest causes of rupture were neglected shoulder presentation (63.2%), brow and face presentations (29.8%) . The age of the patients ranged from 16 to 59 years, with a peak incidence (42 (73.7%)) occurring between 25 and 34 years . Three patients had repair operation and fifty four had hysterectomy . The antibiotics used for treatment of associated infections were crystalline penicillin, ampicillin and chloramphenicol since other drugs were not availablePIP: During September 1989 to August 1992, in South Shoa, Ethiopia, 57 cases of uterine rupture were admitted to Shashemene General Hospital . During the same time period, there were 2185 deliveries, for a uterine rupture incidence rate of 2.6% . 89.4% of uterine rupture cases came to the hospital from distant rural areas . Only 2 of the cases had prenatal care, and they did not die . The age of the 57 women ranged from 16 to 50 . 73.7% of all uterine rupture cases were 25-34 years old . The case fatality rate was 15.8% (9 cases) . 94.7% of all uterine rupture cases were parity 3 or above . 85.9% of all cases had lateral wall uterine rupture . The leading causes of uterine rupture were neglected shoulder presentation (63.3%) and brow and face presentation (29.8%) . The most common post-operative complication was wound infection (22.8%) . Among survivors, the mean duration of hospitalization was 13 days (6 hours to 20 days) . 54 patients underwent hysterectomy . Physicians prescribed crystalline penicillin, ampicillin, and chloramphenicol for treatment of associated infections . Int J Dev Neurosci, 1995 Oct, 13(6), 655 - 8 Effect of early cortical lesion on the acute model of epilepsy; Culic M et al.; The experiments were performed in order to investigate the sparing of function following early postnatal cortical lesion in the acute rat model of epilepsy . Sensorimotor cortex was unilaterally removed at 9 and 10 days of postnatal age in lesioned animals, while control animals were only sham operated (at the same early stage of life) or non-operated (before implantation of the electrodes) . Seizure activity was recorded by means of electroencephalograms at adult stage of life induced by parenteral administration of penicillin (1,000,000 I.U./kg, i.p.) . Our results showed that when the cortical lesion was performed in infancy (on the contrary to the lesion performed in adulthood) there was no prolongation of seizure activity in an acute model of epilepsy. An Med Interna, 1995 Oct, 12(10), 508 - 12 {Neurologic manifestations of Whipple disease}; Alba D et al.; Pure neurologic Whipple's disease (WD) may be suspected by same clinical data (dementia-ophthalmoplegia-myoclonus triad, oculomasticatory myorhythmia) with support of MRI . Diagnosis is confirmed by intestinal and/or brain biopsy . Early recognition is critical in a disease that can lead to irreversible neurologic sequelae and that can potentially be cured . Despite therapy, relapses in patients with WD are common, being neurologic recurrence the most frequent and serious . Antibiotics that do not cross the blood-brain barrier are not adequate initial therapy for WD, because they predispose to neurologic relapse . Patients with WD should be treated for one year with antibiotics that cross the blood-brain barrier (such as parenteral penicillin+streptomycin, followed by oral trimethoprim-sulfamethoxazole) . CNS relapse is usually resistant to therapy. Biochem J, 1995 Oct 1, 311 ( Pt 1), 155 - 60 Regulation of the beta-lactamase BlaL of Streptomyces cacaoi: the product of the blaB regulatory gene is an internal membrane-bound protein; Magdalena J et al.; The beta-lactamase-encoding gene blaL, cloned from Streptomyces cacaoi in Streptomyces lividans, is inducible by beta-lactam compounds . This regulation has been shown to depend on the products of two open reading frames, ORF1 (blaA) and ORF2 (blaB) {Lenzini, Magdalena, Fraipont, Joris, Matagne and Dusart (1992) Mol . Gen . Genet . 235, 41-48} . BlaA belongs to the LysR family of transcription activators, whereas BlaB shares some features with the penicillin-recognizing proteins . BlaB has now been overexpressed in Escherichia coli, purified and used for antibody preparation . Immunoblotting of cell-fractionated materials from S . cacaoi showed that BlaB is attached to the internal face of the cytoplasmic membrane . It could not be released by high salt concentrations or EDTA, but only by protease treatment . Under the assay conditions, BlaB did not act as a penicillin-binding protein, a beta-lactamase, a D-amino-peptidase or a target in a phosphorylation step. J Exp Med, 1995 Oct 1, 182(4), 1037 - 43 Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides; Spellerberg B et al.; The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma . Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis . By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size . Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma. Genitourin Med, 1995 Oct, 71(5), 275 - 9 Similar serological response to conventional therapy for syphilis among HIV-positive and HIV-negative women; Goeman J et al.; OBJECTIVES--To compare characteristics of syphilis serological reactivity in HIV positive (+) and HIV negative (-) female sex workers, as well as the serological response to therapy after treatment with intramuscular benzathine penicillin, 2.4 million U weekly, for three consecutive weeks . METHODS--Rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) results of 72 HIV-positive and 121 HIV-negative women reactive in both tests were assessed . The response to therapy was prospectively monitored with quantitative RPR serology in 47 HIV-positive and 73 HIV-negative patients . Cumulative probabilities of becoming nonreactive by RPR were compared at six months, one and two years after therapy . RESULTS--At enrolment, the geometric mean titres of RPR and TPHA were lower in HIV-positive patients (RPR, 1:2.6) than in HIV-negative patients (RPR, 1:3.8; p < 0.01) . The evolution over time of RPR titres was similar among HIV-positive patients as compared to HIV-negative patients . Among patients with an initial RPR titre of < 1:8, 53% of HIV-positive and 44% of HIV-negative patients became RPR negative two years after therapy . Among patients with an RPR titre of 1:8 or greater at enrolment, 83% of HIV-positive and 90% of HIV-negative patients had reached at least a fourfold decline of RPR titres two years after therapy . CONCLUSIONS--Syphilis serology findings (both RPR and TPHA) may be altered in the presence of HIV infection, but the serological response to therapy was similar in HIV-positive and HIV-negative patients. J Biotechnol, 1995 Sep 29, 42(2), 95 - 107 Continuous cultivation of Penicillium chrysogenum . Growth on glucose and penicillin production; Christensen LH et al.; A series of constant-mass, continuous cultivations of the penicillin producing mold Penicillium chrysogenum was carried out using a chemically defined medium with glucose as the growth-limiting component . The stoichiometry for growth of P . chrysogenum on glucose was characterized in terms of mass-yield and maintenance coefficients . Saturation kinetics with respect to glucose was used to describe the glucose consumption rate at steady-state conditions . Transient data indicate that the maximum rate of glucose consumption at a particular set of operating conditions is correlated to the metabolic 'capacity' of the mold as reflected by its intracellular RNA content . A progressive loss in the penicillin productivity in glucose limited chemostat cultures was correlated to the formation of two mutants . The two mutants were characterized by their sporulation when grown as surface cultures and by Southern dot-tests for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin-N synthase (IPNS) and acyl-CoA:6-APA acyltransferase (AT) . The loss of penicillin productivity was caused by an increasing fraction of mutants which had lost the genes encoding for all three enzymes needed in the penicillin synthesizing pathway. Biochemistry, 1995 Sep 19, 34(37), 11660 - 7 Mass spectral kinetic study of acylation and deacylation during the hydrolysis of penicillins and cefotaxime by beta-lactamase TEM-1 and the G238S mutant; Saves I et al.; The G238S substitution found in extended-spectrum natural mutants of TEM-1 beta-lactamase induces a new capacity to hydrolyze cefotaxime and a large loss of activity against the good substrates of TEM-1 . To understand this phenomenon at the molecular level, a method to determine the acylation and deacylation elementary rate constants has been developed by using electrospray mass spectrometry combined with UV spectrophotometry . The hydrolysis of penicillins and cefotaxime by TEM-1 and the G238S mutant shows that the behavior of penicillins and cefotaxime is very different . With both enzymes, the limiting step is deacylation for penicillin hydrolysis, but acylation for cefotaxime hydrolysis . Further analyses of the G238S mutant show that the loss of activity against penicillins is due to a large decrease in the deacylation rate and that the increase in catalytic efficiency against cefotaxime is the result of a better Km and an increased acylation rate . These modifications of the elementary rate constants and the hydrolytic capacity in the G238S mutant could be linked to structural effects on the omega-loop conformation in the active site. Ukr Biokhim Zh, 1995 Sep-Oct, 67(5), 32 - 42 {Phosphorus-containing inhibitors of penicillin acylase . 4 . Irreversible inhibition of penicillin acylase from Escherichia coli by monoaryl esters of benzylphosphonic acid}; Solodenko VA et al.; Monoaryl of benzylphosphonic acid have been synthesized and studied as the inhibitors of penicillin acylase . These compounds were found to be effective and selective irreversible inhibitors of the enzyme . The kinetic parameters of enzyme inactivation are determined, and possible mechanism of the inhibition is discussed . These phosphonates should be useful as both penicillin acylase active site titrants and the tools for the enzyme function study . Benzylchloromethyl keton has been also prepared and it is an irreversible inhibitor of penicillin acylase. Ukr Biokhim Zh, 1995 Sep-Oct, 67(5), 29 - 32 {Inhibition of penicillin acylase from Escherichia coli by benzylalkylketones and benzylalkylcarbinols}; Tserniuk VN et al.; A number of benzylalkylketones and benzylalkylcarbinols have been synthesized as non-hydrolizable substrate analogues of penicillin acylase (EC 3.5.1.11), and their affinity to the enzyme has been studied . The compounds with plane trigonal carbonyl group (ketones) were established to has bind to the enzyme 20-40 times more tightly than their tetrahedral counterparts with a hydroxyl function (carbinols) . 4-Oxo-5-phenylpentanoic acid was found to be one of the most potent reversible competitive inhibitors of penicillin acylase with Ki-31 microM. J Investig Allergol Clin Immunol, 1995 Sep-Oct, 5(5), 276 - 82 Hypersensitivity reactions to drugs: correlation between clinical probability score and laboratory diagnostic procedures; Perez T et al.; The in vitro diagnosis of allergic drug reactions have not made significant progress in recent years . Specific stimulation of lymphocytes from allergic patients represents an approach to demonstrating sensitization to the implicated drug . So far, skin tests and RAST can only be applied to a limited number of situations . The purpose of this study was to standardize the clinical criteria in order to establish a clinical probability score for each drug . Independently, the various laboratory procedures mentioned were compared with the established clinical probability score for each drug . The results showed that, for the few common drugs studied, the correlation between the clinical probability score and the results of the in vitro lymphocyte transformation test was significant . A significant correlation between the clinical probability score and the skin tests was only shown for penicillin and its derivatives. Arq Neuropsiquiatr, 1995 Sep, 53(3-A), 498 - 502 {Actinomycotic abscess of the cerebellum: a case report}; Tsubouchi MH et al.; A 38 year-old man presented fever and a clinical picture of intracranial hypertension and ataxic syndrome . A CT-scan disclosed an expanding lesion of the cerebellum . Surgical excision of the lesion was performed and pathological examination made the diagnosis of an actinomycotic abscess . The probable primary source of infection were the lungs and/or oral cavity . The postoperative course was uneventful, with complete recovery after a long period of treatment with penicillin (IV and PO) . The authors review some aspects about central nervous system involvement in actinomycosis. Arq Neuropsiquiatr, 1995 Sep, 53(3-A), 494 - 7 {Atypical neurosyphilis: report of a case}; Gastal FL et al.; The present study is based on the observation of a case at the inpatient service of Clinica Olive Leite in August 1992 . A 31 years old female patient, showing cognitive deterioration and dementia syndrome associated with paranoid elements (hallucination and delirium), was admitted as a case of organic psychosis . Diagnostic investigation evidenced positive tests for syphilis in serum and cerebrospinal fluid . The following peculiar aspects are emphasized in this case: severe clinical presentation, severe presentation symptoms (amaurosis and a severe cognitive deficit), sex, age, and for being the first case diagnosed in the service since 1968 (occasion in which the last neurosyphilis case was registered in its data bank) . In the following nine months, after penicillin therapy, the patient showed some improvement characterized by a reduction of productive symptoms of hallucination and delusion type, reduction of the cognitive deficit, and a higher production of the social behavior activities. Neuropeptides, 1995 Sep, 29(3), 163 - 70 Penicillin-G induced interictal activity increases both opioid peptide tissue content and in vitro release in the rat brain; Asai M et al.; Penicillin-G has been used as a common agent to produce epileptic foci and interictal activity . The development of the interictal spikes has been associated with enhanced inhibitory effects . There is evidence that the opioid peptides play an important role in the production of some transient postictal behaviors . In order to test whether enkephalins are involved during the interictal activity, we analyzed immunoreactive met- and leu-enkephalin content and their release in vitro, after the injection of 50 IU of penicillin-G into the left amygdala . Male Wistar rats were injected once daily for 5 days, and sacrificed by decapitation (15 min after the penicillin-G infusion) on the fifth day . The rats were divided into two groups: 1 . In one group we analyzed the tissue content of enkephalins in hypothalamus, hippocampus, amygdala, striatum and cerebral cortext . 2 . The second group was used for the assessment of the in vitro release of enkephalins from amygdala slices . In the amygdala, the drug treatment produced an increase in the tissue content of IR-ME . No changes occurred in the other structures . The content of IR-Leu-enkephalin increased in all structures analyzed except the cerebral cortex . In vitro release of both enkephalins increased in drug treated animals . These results suggest that the enkephalins could be involved in postictal mechanisms, as a result of repetitive interictal spiking. J Immunol, 1995 Sep 1, 155(5), 2670 - 8 Heterogeneous T cell responses to beta-lactam-modified self-structures are observed in penicillin-allergic individuals; Brander C et al.; To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself or penicillin G coupled with human serum albumin (BPO-HSA) . T cell clones specific for penicillin G or BPO-HSA were established and their phenotype and reactivity to both forms of the beta-lactam were analyzed . T cell clones stimulated by penicillin G were CD4 and CD8 positive, whereas BPO-HSA stimulated the growth of CD4+ T cells . The penicillin G-specific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G . In contrast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones . In addition to classical APC, activated MHC class II expressing T cells could also restimulate the penicillin G-specific clones, indicating that various cell types might serve as APC . Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokine pattern as most clones produced high amounts of IL-2, IFN-gamma, TFN-alpha, and rather variable levels of IL-4 and IL-5 . Since no Ag processing was required, penicillin G may stimulate T cells by binding directly to MHC molecules on the cell surface or to their embedded peptide . Alternatively, it may bind to soluble proteins like HSA, which are processed and subsequently presented in an immunogenic form . These different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy. J Inorg Biochem, 1995 Sep, 59(4), 827 - 33 Metal ion interaction with penicillins--Part VII: Mixed-ligand complex formation of cobalt(II), nickel(II), copper(II), and Zinc(II) with ampicillin and nucleic bases; Mukherjee G et al.; Equilibrium study on the mixed-ligand complex formation of M2+ ions (M = Co, Ni, Cu, and Zn) with alpha-d-(-)aminobenzyl penicillin popularly known as ampicillin, (hereafter, ampH +/-), and nucleic bases, viz . adenine, guanine, thymine, uracil, and cytosine (B), in aqueous solution at 37 degrees C at a fixed ionic strength, I = 0.1 M (NaNO3) indicates the formation of complexes of the types: M(amp), M(B), M(amp)(B), M(H-1 amp)(B), and M(H-1 amp)(B)(OH) . Stability constants of the ternary complexes are in the order: Co2+ < Ni2+ < Cu2+ > Zn2+ with regard to the mental ions and guanine > adenine > uracil > thymine > cytosine with regard to the nucleic bases . Complex formation equilibria have been worked out on the basis of species distribution curves. Int J Dermatol, 1995 Sep, 34(9), 627 - 9 Immediate nonallergic psychotic reaction to intramuscular procaine penicillin; Einterz EM et al.; BACKGROUND . Though little known by medical personnel, an immediate nonallergic psychotic reaction to intramuscular procaine penicillin has been reported occasionally from many countries since 1951 . MATERIALS AND METHODS . A case report describes a patient whose violent behavior, provoked by this reaction, resulted in legal action taken against him . Two other nonviolent cases are presented and are followed by a review of the literature . RESULTS . Signs and symptoms of this reaction that appears to be to the procaine component resemble a pressor response and are therefore contrary to the signs and symptoms of an anaphylactic reaction . Anxiety, hallucinations, hypertension, and tachycardia are characteristic . The reaction is self-limited . Long-term psychologic sequelae might be averted by adequate reassurance . CONCLUSIONS . The importance of procaine penicillin as an essential drug in many parts of the world should not be diminished; however, recognition of acute nonallergic psychotic reactions is of paramount importance to assure proper patient management and to avoid misinterpretation of aggressive behavior. Eur J Immunol, 1995 Sep, 25(9), 2486 - 91 Activation and hapten inhibition of mast cells sensitized with monoclonal IgE anti-penicillin antibodies: evidence for two-site recognition of the penicillin derived determinant; Fernandez M et al.; We utilized an in vitro mast cell activation assay and hapten inhibition of mediator release to characterize the fine specificity of two IgE anti-penicillin monoclonal antibodies (mAb) . Cultured mouse mast cells were passively sensitized with IgE mAb anti-benzylpenicillin (BP) or anti-amoxicillin (AX) and challenged with a range of penicillin-human serum albumin (HSA) conjugates . Mast cells sensitized with IgE anti-BP degranulated in response to BP-HSA, but not to AX-HSA or ampicillin(AMP)-HSA, whereas mast cells sensitized with IgE anti-AX responded to AX-HSA but not to BP-HSA or AMP-HSA . Because BP, AX and AMP differ chemically only in the structure of their side chain, these results show that this part of the drug molecule is essential for recognition by IgE antibody . Unexpectedly, although IgE-sensitized mast cells responded to only one penicillin in protein-conjugated form, antigen-induced degranulation was inhibited by the monomeric derivative of more than one penicillin . Furthermore, antigen activation of IgE-sensitized cells was inhibited, although less potently, by haptens representative of the specific penicillin side chain or the binuclear portion of the drug molecule . These patterns of recognition and hapten inhibition were also seen in solid-phase enzyme-linked immunosorbent assay (ELISA), although all haptenic inhibitors were approximately 100 times less potent in the ELISA compared to the mast cell assay . To explain these findings we propose a model in which IgE binding to penicillin-protein antigen is dependent on recognition of two distinct epitopes on the drug molecule: the first comprising the side chain, and the second comprising the binuclear portion plus the proximal region of the side chain . This two-site hypothesis provides a generally applicable model of antibody recognition of penicillins and provides a rational basis for understanding the specificity and cross-reactivity of IgE-mediated allergic reactions to penicillins. Boll Chim Farm, 1995 Sep, 134(8), 467 - 71 Stability study of azlocillin sodium in glass bottles and PVC bags containing intravenous admixtures; Puiggros Boldu S et al.; The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated at different temperatures . The effect of temperature has been determined and from this data, by applying of Arrhenius-law, the stability of azlocillin sodium at 25 degrees C has been predicted and the t90 was determined . Admixtures containing azlocillin sodium (0.01 g ml-1) were prepared in 0.9% sodium chloride injection, in 5% dextrose solution, in 5% levulose solution and in Ringer's lactate solution . The admixtures were stored at 30 degrees, 40 degrees and 50 degrees C in either polyvinyl chloride bags and glass bottles . The change in the initial azlocillin sodium concentration was related to the type of intravenous solution . No dependence with material of container was found . After 24 hours, the change in the initial concentration of penicillin was less than 10% of the initial concentration in 0.9% sodium chloride and 5% levulose solution . However in Ringer's lactate and 5% glucose solution the t90 was lower . These results were found in agreement with experimental ones obtained at room temperature. J AOAC Int, 1995 Sep-Oct, 78(5), 1144 - 52 Comparison of four commercially available rapid test kits with liquid chromatography for detecting penicillin G residues in bovine plasma; Boison JO et al.; Four commercially available rapid tests (Brilliant Black reduction test, LacTek test, Charm Farm test, and Charm Test II receptor assay) were compared with a liquid chromatographic (LC) method (lowest quantitatable level of 5 ng/mL) in their efficiency, reliability, and sensitivity to detect penicillin G in bovine plasma . Samples were obtained from 16 steers treated with procaine penicillin G alone or in combination with its long-acting form, benzathine penicillin G . The steers were injected intramuscularly with penicillin G doses ranging from label dose to about 9 times label dose . When results of the Brilliant Black reduction, LacTek, Charm Test II, and Charm Farm tests for penicillin G in plasma (with detection sensitivities of 5, 10, 20, and 30 ng/mL, respectively) were compared with results of LC, none of the rapid tests gave false-positive results . Each rapid test elicited a positive response when used to test bovine plasma containing penicillin G residues at concentrations above the test's detection sensitivity . The simplicity, selectivity, and sensitivity of the rapid tests, coupled with rapidity with which results are obtained, make them suitable for use in large-volume preslaughter screening of penicillin-treated cattle. Int Arch Allergy Immunol, 1995 Sep, 108(1), 74 - 81 Studies of the specificities of IgE antibodies found in sera from subjects with allergic reactions to penicillins; Moreno F et al.; Penicillins are immunogenic when administered to humans and in some instances they can also be allergenic, inducing specific IgE antibodies . Whilst the major haptenic group, the penicilloyl, is well characterised, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response . In order to investigate this further, sera from subjects who had suffered an IgE-mediated reaction to penicillins were studied using the radioallergosorbent test (RAST) and RAST inhibition . The assays employed reagents related to the penicillins causing the reaction . Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (AX) . Fifty-three positive sera were selected for further studies and categorized into three groups: (A) sera only RAST positive to AX, (B) sera only positive to BP and (C) sera positive to both penicillins . RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structures of BP and AX . For all three groups, monomeric penicilloyl conjugates were the most efficient inhibitors but there were differences for the other compounds . Group A sera were also inhibited by the side chain amoxicillin, whereas group B sera were poorly inhibited by all other inhibitors . Group C sera showed two patterns of inhibition, both consistent with their more cross-reactive profile. Neurosci Lett, 1995 Aug 18, 196(1-2), 49 - 52 Effect of neurotoxin DSP4 on EEG power spectra in the rat acute model of epilepsy; Culic M et al.; The effect of the adrenergic neurotoxin N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on electroencephalographic (EEG) activity was studied in the model of epilepsy induced by systemic application of penicillin (1,000,000 IU/kg, i.p) . DSP4 (50 mg/kg, i.p.) was administrated to male Wistar rats, while the control animals were rats from the same litters . EEG activity was recorded in acute and chronic experiments 3 or 4 weeks after DSP4 treatment, before and after penicillin administration . Occasional locus coeruleus (LC) stimulation served as an electrophysiological test of DSP4 toxic effect . EEG power spectra in DSP4 treated animals showed a tendency to be greater in lower frequency bands than in controls before penicillin administration; there was almost no effect of electrical LC stimulation, regardless on penicillin treatment . In the model of epilepsy, the mean total EEG power spectra were greater in the period of 135-330 min after penicillin administration, as well as during 345-540 min, in DSP4 treated animals as compared to the controls . It seems that neurotoxin DSP4 is an optimal tool for studying the removal of LC influence in the acute model of epilepsy . It is also suggested that norepinephrine (NE) may have a modulatory role in the systemic penicillin epilepsy. J Vet Pharmacol Ther, 1995 Aug, 18(4), 260 - 73 Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits; Li T et al.; Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied . Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers . Penicillin (PEN), intramuscularly at 200,000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits . For each drug, 13-18 groups (n = 5-10 individuals/group) of the dosed animals were killed at different post-dosing times . Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures . Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program . Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined . Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6-1.4, 4.7-9.0, 4.5-18.9, 1.8-3.1, 0.9-3.0, 3.4-9.6, 5.0-16.1 and 7.4-12.2 h . The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 microgram/g in various tissues ranged from 5.0-11.6, 70.0-110.5, 114.0-179.8, 21.3-30.3, 4.1-24.8 and 47.8-84.4 h . Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue . It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs . Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals. Gen Comp Endocrinol, 1995 Aug, 99(2), 239 - 47 In vitro secretion of insulin-like growth factor-binding proteins from liver of striped bass, Morone saxatilis; Fukazawa Y et al.; In vitro secretion of insulin-like growth factor-binding proteins (IGFBPs) from liver of striped bass (sb: Morone saxatilis) was studied using a simple organ-culture system . Liver cubes (1 mm3) were cultured in minimum essential medium with Earle's salts containing 0.1% bovine serum albumin and 100 U/ml penicillin in 5% CO2/95% O2 at 16 degrees . The amount of double-stranded DNA in these cultured liver cubes did not change by 192 hr in the culture, but decreased by 216 hr . Four IGFBPs (a 23- to 24-kDa protein, a 28- to 30-kDa protein, a 35- to 39-kDa protein, and an 85- to 90-kDa protein) were identified in striped bass serum by Western ligand blotting; two of these IGFBPs, 23-24 kDa (sbIGFBP-1) and 28-30 kDa (sbIGFBP-2), were consistently detected in culture media by Western ligand blot analysis . The intensity of the blot for sbIGFBP-2 was consistently greater than that of sbIGFBP-1, which was no longer secreted after 96 hr in culture . The effects of hormones and growth factors on IGFBP secretion by liver tissue were measured after 48 hr in culture . sbIGFBP-1 in the medium was significantly decreased by adding ovine prolactin (10 micrograms/ml), bovine insulin (100 micrograms/ml), and bovine IGF-I (100 ng/ml), but was increased by 17 beta-estradiol (E2: 5 and 50 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) J Egypt Soc Parasitol, 1995 Aug, 25(2), 437 - 41 Cultivation of Leishmania sp . in nutrient broth; Ozbilgin A et al.; Bone-marrow aspiration and biopsy material samples obtained from two patients, one diagnosed as visceral and other as cutaneous leishmaniasis, were inoculated in Novy, McNeal, Nicolle (NNN) medium and nutrient broth (NB), containing fetal calf serum (FCS), penicillin and streptomycine . Both media were incubated at 27 degrees C for 10 days and observed daily for L . infantum and L . major promastigotes . Promastigotes were observed in nutrient broth after the first day, while in NNN media after the second or third day of incubation, indicating the effectiveness of nutrient broth in early diagnosis of both forms of leishmaniasis. J Bacteriol, 1995 Aug, 177(15), 4224 - 9 Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate (ppGpp) and penicillin tolerance in Escherichia coli; Rodionov DG et al.; The penicillin tolerance exhibited by amino acid-deprived Escherichia coli has been previously proposed to be a consequence of the stringent response . Evidence indicating that penicillin tolerance is directly attributable to guanosine 3',5'-bispyrophosphate (ppGpp) overproduction and not to some other effect of amino acid deprivation is now presented . Accumulation of ppGpp in the absence of amino acid deprivation was achieved by the controlled overexpression of the cloned relA gene, which encodes ppGpp synthetase I . The overproduction of ppGpp resulted in the inhibition of both peptidoglycan and phospholipid synthesis and in penicillin tolerance . The minimum concentration of ppGpp required to establish these phenomena was determined to be 870 pmol per mg (dry weight) of cells . This represented about 70% of the maximum level of ppGpp accumulated during the stringent response . Penicillin tolerance and the inhibition of peptidoglycan synthesis were both suppressed when ppGpp accumulation was prevented by treatment with chloramphenicol, an inhibitor of ppGpp synthetase I activation . Glycerol-3-phosphate acyltransferase, the product of plsB, was recently identified as the main site of ppGpp inhibition in phospholipid synthesis (R . J . Health, S . Jackowski, and C . O . Rock, J . Biol . Chem . 269:26584-26590, 1994) . The overexpression of the cloned plsB gene reversed the penicillin tolerance conferred by ppGpp accumulation . This result supports previous observations indicating that the membrane-associated events in peptidoglycan metabolism were dependent on ongoing phospholipid synthesis . Interestingly, treatment with beta-lactam antibiotics by itself induced ppGpp accumulation, but the maximum levels attained were insufficient to confer penicillin tolerance. Chirurg, 1995 Aug, 66(8), 823 - 5 {Rare manifestation of actinomycosis as retroperitoneal space-occupying lesion}; Seelig MH et al.; Actinomycosis has to be included in the differential diagnosis of retroperitoneal masses especially when surrounding tissue is infiltrated . We present a 40 year old male patient with the rare manifestation of retroperitoneal actinomycosis . The definitive treatment consisted of surgical drainage and long-term penicillin therapy resulting in complete healing . Special features in clinical symptomatology and problems concerning diagnosis of actinomycosis are discussed. Appl Microbiol Biotechnol, 1995 Aug-Sep, 43(4), 679 - 84 Improvement of the catalytic properties of penicillin G acylase from Escherichia coli ATCC 11105 by selection of a new substrate specificity; Niersbach H et al.; Cloned penicillin G acylase (PGA) from Escherichia coli ATCC 11105 was mutagenized in vivo using N-methyl-N'-nitro-N-nitrosoguanidine . Mutants of PGA were selected by their ability to allow growth of the host strain E . coli M8820 with the new substrates phenylacetyl-beta-alanyl-L-proline (PhAc-beta Ala-Pro) phthalyl-L-leucine (Pht-Leu) or phthalylglycyl-L-proline (Pht-Gly-Pro) as sole source of proline and leucine respectively . PGA mutants were purified and immobilized onto spherical methacrylate (G-gel) . The immobilized form of mutant PGA selected with (PhAc-beta Ala-Pro) hydrolyzed 95% of 9 mmol penicillin G 30% faster than wild-type PGA using the same specific activities . The specific activity of the soluble enzyme was 2.7-fold, and inhibition by phenylacetic acid was halved . Immobilized PGA mutant selected with Pht-Gly-Pro hydrolyzed penicillin G 20% faster than wild-type PGA . The Km of the soluble enzyme was increased 1.7-fold . Furthermore, the latter two mutants were also 3.6-fold more stable at 45 degrees C than wild-type PGA . The specific activity of the mutant selected with Pht-Leu was 6.3-fold lower, and inhibition by phenylacetic acid was increased 13-fold. Allergy, 1995 Aug, 50(8), 671 - 6 Basic aspects related to penicillin-allergy skin testing: on the variability of the hapten-paratope interaction; Bondaruk J et al.; Ampicillin and benzylpenicillin conjugated to human serum albumin were used as immunogens in order to obtain antihaptenic IgG responses in outbred guinea pigs according to different schedules, all involving complete Freund's adjuvant . The individual responses were characterized by ELISA and by ELISA inhibition using ampicillin, benzylpenicillin, and carbenicillin peptidic conjugates for coating and for inhibition . In several instances, drastically reduced cross-reactivity and even its absence were observed, although the penicillin antigens differ only in the side-chain . The notion that the invariantly pr