Penicillin

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 present thiazolidine ring will always provide significant binding to antibodies against all penicillins differing only in the side-chain has to be dropped . The experiments were performed in relation to newer findings of clinical penicillin-allergy skin testing which suggest that benzylpenicillin-based reagents alone are not able to detect or predict all reactions against semisynthetic penicillins . The experimental evidence here obtained corroborates this conclusion.

J Neurophysiol, 1995 Aug, 74(2), 650 - 72
Diverse neuronal populations mediate local circuit excitation in area CA3 of developing hippocampus; Smith KL et al.; 1 . Studies were undertaken to better understand why the developing hippocampus has a marked capacity to generate prolonged synchronized discharges when exposed to gamma-aminobutyric acid-A (GABAA) receptor antagonists . 2 . Excitatory synaptic interactions were studied in small microdissected segments of hippocampal area CA3 . Slices were obtained from 10- to 16-day-old rats . Application of the GABAA receptor antagonist penicillin produced prolonged synchronized discharges in minislices that were very similar, if not identical, to those recorded in intact slices . The sizes of minislices were systematically varied . Greater than 90% of those that measured 600 microns along the cell body layer produced prolonged synchronized discharges, whereas most minislices measuring 300 microns produced only brief interictal spikes . 3 . Action potentials in the majority (75%, 158 of 254) of cells impaled with microelectrodes were able to entrain the entire CA3 population . They were also able to increase (on average 26%) the frequency of spontaneous population discharges . The population discharges were followed by a refractory period that lasted 5-60 s, during which single cells were unable to initiate a population discharge . 4 . The majority (87%) of neurons with intrinsic burst properties were found to entrain the CA3 population . The electrophysiological characteristics of these cells were reminiscent of recordings obtained from more mature rats . Action potentials were quite prolonged and demonstrated a secondary shoulder or hump on the down-slope of the spike . 5 . When bursting cells were filled with Lucifer yellow and imaged during recording sessions by videomicroscopy and later using confocal microscopy, they showed the anatomic features of CA3 hippocampal pyramidal cells . Confocal microscopy permitted detailed characterization of individual neurons and showed substantial variation in cellular microanatomy . 6 . Another class of cells that were found to entrain the CA3 population but did not demonstrate intrinsic bursts were termed regular-firing cells . These cells possessed many of the anatomic and physiological features of bursting cells with the exception of burst firing . They were rarely encountered in intracellular recordings . 7 . The third physiological class of cells was termed fast-spiking cells . These had action potentials that were shorter in duration than the other two cell types . They were distinct in the rapid rate of spike repolarization . They demonstrated modest degrees of spike frequency adaptation and fired repeatedly and at relatively high frequencies . Compared with reports on fast-spiking cells in mature hippocampus and neocortex, action potentials appear to be slower and repetitive discharging appeared to be of a lower frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Ugeskr Laeger, 1995 Jul 31, 157(31), 4350 - 4
{Poisoning by green and white mushrooms at a special hepatology unit, 1989-1994}; Schiodt FV et al.; In the period 1989-1994 eight patients, who were intoxicated with the mushrooms Amanita phalloides (death cap) or Amanita virosa (deadly agaric) were treated at a Department of Hepatology . All patients had had a symptom free period of more than eight hours before the onset of gastrointestinal symptoms; these symptoms lasting in many cases for several days . All patients had biochemical signs of hepatocellular damage and three patients developed hepatic encephalopathy, fulfilling the criteria for fulminant hepatic failure (FHF) . Two died and one patient underwent successful urgent liver transplantation . ALL FHF patients had a prothrombin index below 10% and increased creatine . Antidote treatment with penicillin and silibinine should be given promptly on suspicion of Amanita intoxication and should not await biochemical parameters . Transferral to a hepatological department with access to liver transplantation should be considered if abnormal biochemical liver function develops.

Brain Res, 1995 Jul 24, 686(2), 194 - 206
Chaotic responses of the hippocampal CA3 region to a mossy fiber stimulation in vitro; Hayashi H et al.; Undoubted evidence of chaotic activity of a biological neural network are given . Spontaneous epileptiform bursts of a neuron population in the CA3 region of rat hippocampal slices were caused in a perfusing medium with 2 mM penicillin and 8 mM K+ ions, and responses of field potential in the CA3 region to a periodic mossy fiber stimulation were investigated . Phase-locked and chaotic responses occur depending on stimulus parameters; for example, when the frequency of the stimulation increases, 1:1 phase-locking bifurcates to chaos through 1:2 phase-locking . The chaotic responses show a broad-band spectrum, and their trajectories in the three-dimensional phase space (V(t), V(t + tau), V(t + 2 tau)) reconstruct a strange attractor . Lyapunov exponents of the strange attractors estimated by the Wolf's algorithm are positive . Moreover, one-dimensional strobomaps obtained from the chaotic responses show a non-invertible function . Since the slope of each strobomap at their fixed point is more negative than -1, the fixed points are unstable . These are undoubted evidences for chaotic responses of the CA3 region in hippocampal slices maintained in vitro . Cross-correlation functions between field potential responses which were simultaneously observed at different sites show that the responses are spatially coherent throughout the CA3 region even when the responses are chaotic.

Ann Acad Med Singapore, 1995 Jul, 24(4), 569 - 78
Sexually transmitted diseases in Australia: a decade of change . Epidemiology and surveillance; Mulhall BP et al.; Survival data in the last decade for sexually transmitted diseases (STDs) other than human immunodeficiency virus (HIV) are uneven across the states/territories . The incidence of gonorrhoea decreased by more than 80%, but at different times in different patient groups, different states, and different anatomical sites . There was a resurgence of rectal gonorrhoea in homosexual men in 1989-1991 . Resistance to penicillin steadily increased, and partial resistance to quinolones has emerged . There was a marked decline in syphilis in most states . Lymphogranuloma venereum is rare, and chancroid seen mostly in returning travellers from Southeast Asia; however, hundreds of cases of donovanosis are seen annually among rural Aborigines . The prevalence of genital infections with Chlamydia trachomatis remained stable at 2.5%-14% in STD clinics, and 5% in family planning clinics . The numbers of cases of clinical genital herpes and warts are mostly unavailable . However, specific serology for herpes simplex virus type 2 (HSV-2) indicates that 14% of antenatal clinic patients, and 40%-60% of STD patients have been exposed . Pap smears have detected the presence of human papilloma virus (HPV) in 14%-40% of various clinic populations . Exposure to hepatitis B in the non-Aboriginal population decreased markedly . Hepatitis C infection occurred in a high percentage of injecting drug users; the evidence for sexual transmission is not strong . An epidemic of hepatitis A infection occurred in male homosexuals in 1989-1991 . Changes in the Australian sex industry resulted in marked improvements in the sexual health of local (but not international) sex workers . The high levels of STDs in Aboriginal communities continues to cause concern.

Curr Genet, 1995 Jul, 28(2), 177 - 83
NRE, the major nitrogen regulatory protein of Penicillium chrysogenum, binds specifically to elements in the intergenic promoter regions of nitrate assimilation and penicillin biosynthetic gene clusters; Haas H et al.; NRE, the nitrogen regulatory protein of Penicillium chrysogenum, contains a single Cys2/Cys2-type zinc-finger motif followed immediately by a highly basic region . The zinc-finger domain was expressed to Escherichia coli as a fusion protein with beta-galactosidase . In order to test the putative DNA-binding ability of NRE, the intergenic promoter region of the nitrate reductase/nitrite reductase gene cluster (niiA-niaD) of Penicillium was sequenced . Our results show that NRE is a DNA-binding protein and binds to the intergenic promoter regions of the P . chrysogenum niiA-niaD and acvA-pcbC gene cluster, encoding the first two enzymes in penicillin biosynthesis . Three of the four high-affinity NRE-binding sites contained two GATA core elements . In one of the recognition sites for NRE, one GATA motif was replaced by GATT . The two GATA elements showed all possible orientations, head-to-head, head-to-tail and tail-to-tail, and were separated by between 4 and 27 bp . Missing-contact analysis showed that all three purines in both of the GATA core sequences and the single adenine residue in each of the complementary TATC sequences were involved in the binding of NRE . Moreover, loss of purines in the flanking regions of the GATA elements also affect binding of NRE, as their loss causes reduced affinity.

Allergy, 1995 Jul, 50(7), 563 - 7
Nonimmediate reactions to betalactams: prevalence and role of the different penicillins; Terrados S et al.; In patients treated with penicillins, adverse cutaneous reactions can occur within minutes or may take several days to develop . IgE antibody-mediated reactions are well documented, but other mechanisms may also be involved . In particular, nonimmediate reactions have not been studied extensively, and the purpose of the present work was to establish the incidence of such reactions among a large group of patients and to study the penicillins involved . A total of 380 subjects with a history of a cutaneous reaction following administration of a penicillin antibiotic was included in the study . Skin tests and specific IgE measurements (RAST) were carried out using various penicillins and penicillin-related reagents, and patients were also challenged with various penicillins . In some patients with delayed skin test responses, skin biopsies were carried out . The tests confirmed that 74 subjects (19.4% of total investigated) had suffered a cutaneous reaction to a penicillin derivative, and 29 of these subjects (7.6% of total or 39% of confirmed) showed evidence of having suffered a nonimmediate reaction . The latter group were identified by giving a positive delayed direct challenge, and in 65% of the cases a delayed skin test response was detected . In most cases, these responses were to amino penicillins . Skin biopsies showed a lymphomonocytic cell infiltrate . Nonimmediate reactions to penicillins are a reproducible phenomenon, suggesting that a specific mechanism is responsible . By direct challenge, 93% of responders were positive to amino penicillins (10.3% ampicillin, 82.7% amoxicillin), indicating a major role for these penicillins in nonimmediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Exp Dermatol, 1995 Jul, 20(4), 339 - 40
Selective fixed drug eruption to amoxycillin; Arias J et al.; A selective fixed drug eruption to amoxycillin but not other betalactam drugs is reported . Penicillins are the drugs most frequently implicated in immunological adverse reactions . The most important of these are allergic reactions where an IgE-mediated mechanism is well established . Other immunological mechanisms have been described in reactions, such as haemolytic anaemia, serum sickness, drug-induced nephritis, drug fever and contact dermatitis . Fixed drug eruption (FDE) is a type of drug-induced dermatosis, the immunopathogenesis of which remains unknown . FDE is an uncommon reaction to penicillin derivatives, and very few cases have been reported . We present a case of a selective FDE to amoxycillin (AX), with no reaction to other betalactam drugs . Although one similar case has been reported, the reactivity to other penicillin derivatives was not assessed.

J Invest Dermatol, 1995 Jul, 105(1 Suppl), 95S - 98S
Lymphocyte activation in cutaneous drug reactions; Hertl M et al.; Peripheral blood lymphocytes from both drug-induced immediate and delayed cutaneous hypersensitivity reactions frequently can be stimulated in vitro with the particular culprit drug . Immunohistochemical analysis has identified CD8+ T cells as the predominant epidermal T-cell subset in drug-induced maculopapular and bullous eruptions and in patch-test reactions to beta-lactam antibiotics . Beta-lactam-specific peripheral and epidermal T lymphocytes from bullous exanthems were predominantly T-cell receptor alpha/beta+, CD8+, CD4- . Three CD8+ epidermal T-cell clones from penicillin-induced bullous exanthems displayed a TH1-like cytokine pattern and proliferated in an antigen- and major histocompatibility complex-specific manner . These epidermal T-cell clones were cytotoxic against autologous B cells upon stimulation through the T-cell receptor and against epidermal keratinocytes in lectin-induced cytotoxicity assays . In contrast, peripheral T-cell lines from patients with penicillin-induced urticarial exanthems were predominantly T-cell receptor alpha/beta+, CD4+, CD8- and displayed a Th2-like cytokine pattern . CD8+ dermal T cells from a sulfamethoxazole-induced bullous exanthem proliferated in vitro in response to sulfamethoxazole . This T-cell proliferation was significantly increased in the presence of microsomes, which suggests that microsomal enzymes, such as cytochrome P450 enzymes, generate highly reactive metabolites which are the nominal antigens for T-cell activation . In summary, drugs may be processed and presented in different ways, which is reflected by the observation that Th1-like CD8+ T cells are primarily activated in delayed cutaneous hypersensitivity reactions, whereas Th2-like T-cell responses are present in patients with drug-induced urticarial exanthems.

Isr J Med Sci, 1995 Jul, 31(7), 432 - 5
Can an educational program improve the diagnosis and treatment of pharyngotonsillitis in the ambulatory care setting?
Raz R, Porat V, Ephros M.
The influence of an educational program on the diagnosis and treatment of pharyngotonsillitis was evaluated in three outpatient clinics in northern Israel during two periods . During both periods--1 January to 31 March 1988 (baseline phase) and 1 January to 31 March 1989 (study phase)--clinical data of all patients for whom antibiotics were prescribed were recorded on special forms, which included the patient's diagnosis and the antibiotic prescribed . In November 1988, 2 months before the study phase, two 1 h sessions on pharyngitis were given by the study physicians to the entire medical staff of two clinics (Clinics B and C), and written material was distributed . A third clinic (Clinic A) served as the control . A comparison of the prescribing habits during the two phases showed that during the study phase the total number of antibiotics prescriptions for pharyngitis declined significantly in Clinics B and C, while the percentage of prescriptions for penicillin V rose with the concomitant decline of amoxycillin . There were no significant changes in prescribing habits in the control clinic . These results show that a modest 2 h educational program involving direct contact with the entire medical staff of the community outpatient clinics can improve the diagnosis of pharyngotonsillitis and reduce both the inappropriate use of antibiotics in general, and the substitution of more expensive antibiotics for cheaper, equally effective ones.

Am J Med, 1995 Jul, 99(1), 55 - 63
Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy; Malone JL et al.; OBJECTIVE: To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV) . PATIENTS AND METHODS: Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program . RESULTS: Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis . Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy . Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses . The mean CD4+ T-lymphocyte count was not predictive of relapse . Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients {57%}) or the rash of secondary syphilis (4 of 14 patients {29%}) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years . CONCLUSION: Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers . Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

Eksp Klin Farmakol, 1995 Jul-Aug, 58(4), 12 - 3
{Changes in the activity of an epileptogenic focus in the rat hippocampus under the influence of bemitil}; Mikhailov IB et al.; Experiments performed on male rats with chronically implanted electrochemotrodes showed bemitil (12.5 and 25.0 mg/kg, intra-abdominally, 24 h prior to the locus creation) suppresses he pathological activity of (100 ED) epileptogenic locus induced by he sodium salt of penicillin in the hippocampus of the animals . Probable mechanisms of antiepileptic action of bemitil are considered.

Neurol Med Chir (Tokyo), 1995 Jul, 35(7), 462 - 6
Cerebral gumma mimicking glioblastoma on magnetic resonance images--case report; Uemura K et al.; A 39-year-old female presented with a syphilitic cerebral gumma mimicking small glioblastoma multiforme manifesting as visual impairment . Magnetic resonance imaging showed a low signal intensity area on T1-weighted images and marked small ring-like enhancement less than 1 cm in diameter following the administration of gadolinium . The symptoms and radiological abnormalities improved several weeks after penicillin therapy . The small ring-like enhancement was probably caused by inflammation associated with treponemal infection . A mass with a small ring-like enhancement less than 1 cm in diameter is a useful finding indicating an inflammatory lesion rather than a glial tumor.

Proc Natl Acad Sci U S A, 1995 Jun 20, 92(13), 6200 - 4
The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences; Fierro F et al.; The penicillin biosynthetic genes (pcbAB, pcbC, penDE) of Penicillium chrysogenum AS-P-78 were located in a 106.5-kb DNA region that is amplified in tandem repeats (five or six copies) linked by conserved TTTACA sequences . The wild-type strains P . chrysogenum NRRL 1951 and Penicillium notatum ATCC 9478 (Fleming's isolate) contain a single copy of the 106.5-kb region . This region was bordered by the same TTTACA hexanucleotide found between tandem repeats in strain AS-P-78 . A penicillin overproducer strain, P . chrysogenum E1, contains a large number of copies in tandem of a 57.9-kb DNA fragment, linked by the same hexanucleotide or its reverse complementary TGTAAA sequence . The deletion mutant P . chrysogenum npe10 showed a deletion of 57.9 kb that corresponds exactly to the DNA fragment that is amplified in E1 . The conserved hexanucleotide sequence was reconstituted at the deletion site . The amplification has occurred within a single chromosome (chromosome I) . The tandem reiteration and deletion appear to arise by mutation-induced site-specific recombination at the conserved hexanucleotide sequences.

FEMS Microbiol Lett, 1995 Jun 15, 129(2-3), 215 - 20
Depletion of anionic phospholipids has no observable effect on the anchoring of penicillin binding protein 5 to the inner membrane of Escherichia coli; Harris F et al.; Escherichia coli penicillin-binding protein 5 (PBP5) is anchored to the periplasmic face of the inner membrane via a C-terminal amphiphilic alpha-helix . The results of washing experiments have suggested an electrostatic contribution to the anchoring mechanism which may involve the cationic region of the C-terminal alpha-helix . Similarities between this anchor domain and some surface active agents, such as melittin, suggest that the cationic region of the PBP5 anchor may require the presence of anionic phospholipids for membrane interaction . Washing experiments performed on membranes of HDL11, an E . coli mutant in which the expression of the major anionic phospholipids is under lac control, found no such requirement . The results are discussed in relation to the hypothesis that the cationic region may interact with other sources of negative charge, possibly arising from a PBP complex.

Biochemistry, 1995 Jun 13, 34(23), 7757 - 64
Role of asparagine 152 in catalysis of beta-lactam hydrolysis by Escherichia coli AmpC beta-lactamase studied by site-directed mutagenesis; Dubus A et al.; The role of asparagine 152 in the catalytic mechanism of Escherichia coli AmpC beta-lactamase has been investigated by site-directed mutagenesis . The residue has been replaced by aspartic acid, glutamic acid, histidine, and leucine . All the substitutions had similar effects on the activity toward substrates and inhibitors . The rate of substrate hydrolysis decreased by factors of 500-5000 . The rates of both acylation (2-50-fold decrease) and deacylation (50-500-fold decrease) were affected, indicating a role for Asn152 in both processes . The wild-type AmpC beta-lactamase appears to exist as an equilibrium mixture of two forms, identified by their different kinetic properties . The Asn152 mutations affected the activity of the slow-reacting form much more than that of the fast-reacting form, but they did not appear to affect the interconversion of these two kinetic forms . Comparison of these observations with results obtained with mutation of the equivalent residues in other classes of penicillin-sensitive enzyme indicates that there are quite profound differences between the catalytic mechanisms of these enzymes despite a high degree of conservation of amino acids in the active center, and of the overall three-dimensional structure.

Presse Med, 1995 Jun 10, 24(21), 989 - 91
{Spondylodiscitis caused by Fusobacterium nucleatum . Apropos of a case}; Soubrier M et al.; Spondylodiscitis is rarely caused by anaerobic germs and occurs mainly in patients weakened by another infection . We report a case of Fusobacterium nucleatum spondylodiscitis in a 63-year-old man . This is the third such report and the second in a non-immunodepressed patient . The clinical presentation and laboratory findings in this type of spondylodiscitis vary little from those produced by other germs . Magnetic resonance imaging is the most useful diagnostic tool for spondylodiscitis . The germ is isolated from a discal puncture aspirate in 66% of the cases but can also be obtained from blood cultures . Anaerobic germs are usually sensitive to penicillin or cephalosporins.

South Med J, 1995 Jun, 88(6), 647 - 50
Intramural gastric actinomycosis; Skoutelis A et al.; We report a case of intramural gastric actinomycosis and review the features of the additional 16 cases of this uncommon infection reported in the literature . The patient had gastrointestinal symptoms, weight loss, and fever after gastric operation . At laparotomy, an infiltrating gastric tumor-like lesion was found . Histology revealed actinomycosis, and the patient was successfully treated with oral penicillin . Because of its rarity, intramural actinomycosis is an entity overlooked by most surgeons . Reporting of such cases may help increase the awareness of this important and curable disease.

Pediatr Clin North Am, 1995 Jun, 42(3), 509 - 17
The problem of resistant bacteria for the management of acute otitis media; Barnett ED et al.; The emergence of pneumococci resistant to penicillin has prompted an examination of the role of resistant organisms in the response to treatment for AOM . At this time, antibiotic-resistant organisms play a small role in the number of episodes of AOM that do not respond to initial therapy . Amoxicillin remains the drug of choice for treatment of AOM . For children who do not respond, assessment of clinical status is important . Children who are well-appearing may respond to a beta-lactamase stable oral agent . Children who are ill may require tympanostomy and presumptive therapy for infection due to resistant organisms.

Farmaco, 1995 Jun, 50(6), 455 - 69
Design, synthesis and evaluation of D,D-peptidase and beta-lactamase inhibitors: azapeptides, oxapeptides and related heterocycles; Marchand-Brynaert J et al.; Reactive molecules susceptible to form stable acyl enzyme intermediates with D,D-peptidases and beta-lactamases were designed as potential irreversible inhibitors of Penicillin Sensitive Enzymes (PSEs) . The structures examined were a series of azapeptides and oxapeptides, both analogs of the D-Ala-D-Ala substrate, and some heterocycles, such as imidazolidinones and oxazolidinones, both analogs of the beta-lactam antibiotics . The various strategies investigated for their synthesis are described and discussed . Some biological results are reported.

Laryngorhinootologie, 1995 Jun, 74(6), 380 - 4
{Morphologic and immunohistochemical studies of organ cultures of human tracheal biopsies}; Haas I et al.; Most likely the transformation of epithelial cells to carcinoma cells takes place during the process of differentiation . In order to study in vitro carcinogenesis, an experimental system for organ cultures was developed in which human respiratory epithelial from tracheal biopsies differentiate within six weeks . The mucosal and submucosal layer of small tracheal biopsies was cut into pieces measuring 3 x 3 and 5 x 5 mm2, respectively, and placed on Gelita cubes (Braun-Melsungen, Germany) measuring 10 x 10 x 10 mm3 with the epithelium facing up . The culture medium (RPMI 1640 supplemented with 10% fetal calf serum, 200 mM L-glutamine, 100 IU/ml penicillin, and 100 micrograms/ml streptomycin) was added in a way that the tissue lay between the medium and air . Gelita deteriorates in about two to three weeks . However, the cultures are easily transferred to fresh Gelita cubes using the rest of the old Gelita . These organ cultures were fixed at regular intervals, and histological sections were stained with hematoxylin eosin or monoclonal antibodies against cytoskeletal intermediate filament proteins . These morphological and histological studies revealed that the epithelial cells differentiated under these conditions in at least 39 days . The mesenchymal elements remained viable without showing strong proliferation . The implication of these techniques for studying carcinogenesis in vitro is discussed.

Int J Dermatol, 1995 Jun, 34(6), 403 - 7
Malignant syphilis (lues maligna) and concurrent infection with HIV; Don PC et al.; BACKGROUND . During the past 2 1/2 years we observed six patients who had a reactive serology for syphilis, of which four developed widespread noduloulcerative and two vesiculonecrotic lesions . The purpose was to report the occurrence of lues maligna, a rare form of secondary syphilis, in five patients infected with the human immunodeficiency virus (HIV) and in one patient with risk factors for infection . METHODS . Tzanck preparations, viral cultures, and skin biopsies were performed to evaluate the etiology of the lesions . RESULTS . Syphilis serology titers ranged from 1:32 to 1:128 and in one instance was as low as 1:8 . Such titers can also be found in patients with the latent form of syphilis . Therefore, confirmation of the clinical diagnosis of lues maligna was dependent on skin biopsies that were compatible with secondary syphilis and negative viral studies that excluded varicella, disseminated varicella-zoster or herpes simplex . Lues maligna takes an aggressive course in HIV-infected patients since four of the patients required hospitalization and the two patients who refused to complete treatment, subsequently developed more severe skin and constitutional symptoms . CONCLUSIONS . HIV-infected patients are at risk for developing lues maligna . Despite its malignant presentation, lues maligna lesions respond rapidly to treatment with penicillin . Secondary syphilis should be added to the list of diseases known to be more aggressive in HIV-infected patients.

J R Soc Health, 1995 Jun, 115(3), 156 - 8
Sickle cell anaemia in Saudi-Arabian children; Pejaver RK et al.; Forty-one Saudi Arabian children aged between six months and 13 years had a total of 68 admissions for complications of sickle cell anaemia during 1992 . Review of their in-patient records and the relevant out-patient notes revealed a change in the clinical profile as compared to previous years . Hand-foot syndrome is virtually non-existent and vaso-occlusive crisis remains the commonest cause of admission . Introduction of pneumococcal vaccine and prophylactic oral penicillin has had no effect on the frequency of admissions and the admission rate per patient year . We have not seen any septicaemia/meningitis due to pneumococci . No death occurred during 1992.

Hautarzt, 1995 Jun, 46(6), 421 - 4
{Laser Doppler flowmetry in treatment follow-up of circumscribed scleroderma}; Klyscz T et al.; A 38-year-old male patient presented with circumscribed scleroderma (10 x 12 cm) in the left pectoral area . Hyperaemia of the skin in the area of the lilac ring (morphoea) was quantified by means of Laser-Doppler flux (LDF) . At the lilac border of the morphoea LDF was increased to 420% of the reference value recorded for the unaffected skin of the contralateral side . Immediately after 13 days of antibiotic therapy (3 x 10 Mega penicillin G per day, i.v.) LDF normalized, though clinical changes were hardly apparent at this stage . By 6 months later, LDF was still in the normal range, and clinical signs, such as induration and hyperaemic redness, had also significantly improved . LDF measurements allow assessment of the therapeutic response to antibiotic therapy at a very early stage while the clinical situation is still unchanged.

J Antimicrob Chemother, 1995 Jun, 35(6), 883 - 8
Comparative activity of ampicillin, amoxycillin, amoxycillin/clavulanate and cefotaxime against 189 penicillin-susceptible and -resistant pneumococci; Pankuch GA et al.; Agar dilution and E-test MICs of penicillin G, ampicillin, amoxycillin, amoxycillin/clavulanate and cefotaxime were determined against 189 pneumococci . Addition of clavulanate did not influence amoxycillin MICs, MIC50/MIC90 (mg/L) for penicillin G, ampicillin, amoxycillin and cefotaxime were: Penicillin susceptible strains (62): 0.03/0.03; 0.03/0.06; 0.015/0.03; 0.015/0.06 . Penicillin intermediate strains (69): 0.25/1.0; 0.25/4.0; 0.125/1.0; 0.125/1.0 . Penicillin resistant strains (58): 2.0/4.0; 4.0/4.0; 1.0/2.0; 1.0/2.0 . E-test MICs correlated well with those obtained by agar dilution.

Electrophoresis, 1995 Jun, 16(6), 1031 - 3
Transient bisalbuminemia: separation by isoelectric focusing of human albumin fractions linked to different numbers of benzylpenicilloyl groups; Rocha J et al.; The behavior of modified human serum albumin (HSA) from penicillin-treated patients and in vitro conjugated samples was studied by isoelectric focusing in the absence and presence of 8 M urea . It is shown that samples classified as bisalbuminemic after separation under native conditions display a spectrum of several major bands with decreasing pIs when focusing is done in the presence of 8 M urea . In this spectrum, the distances between two consecutive major bands are as expected from a 2-unit charge difference . Since this result is compatible with the blockage of a lysine residue with a benzylpenicilloyl (BPO) group, each major band can be interpreted as representing an HSA fraction covalently linked to different numbers of benzylpenicilloyl groups . The separation methods presented therefore seem to constitute simple and reliable tools for a detailed assessment of the extent of BPO covalent binding to HSA both in vivo and in vitro.

N Z Med J, 1995 May 10, 108(999), 165 - 6
Cutaneous adverse drug reactions in a hospital setting; Rademaker M et al.; AIMS . A prospective survey of the number and nature of cutaneous adverse drug reactions in a hospital setting . METHOD . Six month survey of cutaneous adverse drug reactions in hospital inpatients (April to October 1992) . All patients were reviewed by a specialist dermatologist who assessed the adverse drug reaction as being: (1) type A adverse reaction (ie, expected, eg, acne vulgaris from systemic steroids; (2) type B adverse reaction (ie, unexpected, eg, allergic reaction; (3) not drug related; and (4) other/do not know . RESULTS . Sixty patients were reviewed; 38/60 patients (63%) had a cutaneous reaction related to their drug therapy or in-patient care . Of these, 7 had a nonallergic adverse drug reaction (type A) . A further 31 had a type B adverse reaction: 27 had an allergic reaction to a systemic drug and 4 had an allergic contact dermatitis to a topical agent . 17 patients had cutaneous signs unrelated to their drug therapy, mostly a primary skin disorder (eg, eczema, psoriasis, etc) . Of the remaining 5 patients it was not possible to determine the cause of the cutaneous reaction . The most common drugs associated with adverse drug reactions were the penicillin group of antibiotics, followed by frusemide, prednisone, allopurinol and carbamazepine . CONCLUSIONS . Adverse drug reactions are common and may result in additional morbidity to patients . However, only half of the cutaneous adverse reactions seen were secondary to allergy . As the diagnosis of an allergic reaction to drugs may have important therapeutic implications, review by a specialist dermatologist may be indicated.

J Mol Recognit, 1995 May-Jun, 8(3), 171 - 7
Detection and side-chain specificity of IgE antibodies to flucloxacillin in allergic subjects; Baldo BA et al.; Unlike studies on the antigenicity of penicillins in laboratory animals, limited information is available on the allergenicity of penicillins in man, especially with regard to fine structural allergenic differences between the many different penicillins . Inconsistent with the earlier conclusions of others, our studies suggest that side-chain structures on the penicillin molecule are the major allergenic determinants in many reactions . Immediate allergic reactions to flucloxacillin were observed in a number of patients where diagnosis was confirmed by skin testing and detection of flucloxacillin-reactive IgE antibodies . Quantitative hapten inhibition studies revealed potent inhibition by flucloxacillin and three structurally related penicillins: oxacillin, cloxacillin and dicloxacillin . Analysis of the inhibition results showed that the side-chain group of flucloxacillin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl, is recognized by some antibodies and that the 5-methyl-3-phenyl-4-isoxazolyl group, with or without halogen substituents, accounts for the reactivity of other antibodies and for the cross-reactions seen with some other penicillins . Since it is the side-chain group that distinguishes the many different penicillins, and since the side-chain groups are recognized by IgE antibodies in many of the allergic reactions, it is becoming clear that specific assays are required for the detection of IgE antibodies to each of the different penicillins.

Postgrad Med, 1995 May, 97(5), 45 - 8, 51-2, 55-7
Acute and chronic sinusitis . How to ease symptoms and locate the cause; Ferguson BJ; Patients with acute sinusitis often have purulent nasal discharge, facial pain, and congestion, whereas those with chronic sinusitis have more subtle signs . Infection, hyperreactivity reactions, anatomic obstruction, and underlying disease are among the causes and must be differentiated before appropriate care can be offered . Plain films and sinus transillumination may provide clues in adults but are of little value in young children . Computed tomography is much more sensitive but should be reserved for patients in whom maximal medical therapy has failed, who have a confusing presentation, or who are being considered for endoscopic surgery . Antibiotic therapy is still effective for bacterial infections, but penicillin-resistant organisms are on the increase . If there is no clinical improvement in 3 days, an agent with a broader spectrum of activity should be considered . A combination of agents and prolonged administration may be required for chronic sinusitis, and patients with recurrent symptoms may need endoscopic surgery . Such adjunctive agents as decongestants and saline or steroid nasal sprays may promote drainage . Antihistamines have no role in the treatment of sinusitis.

Ann Plast Surg, 1995 May, 34(5), 493 - 9; discussion 499-500
Dry, moist, and wet skin wound repair; Vogt PM et al.; Effects of wet (saline in a vinyl chamber), moist (hydrocolloid dressing), and dry (sterile gauze dressing) environments on wound repair were studied in a porcine partial-thickness wound model . Chambers were exchanged and refilled daily with normal saline containing penicillin G (100 U/ml) and streptomycin (100 micrograms/ml) . Hydrocolloid and gauze dressings were kept in place until biopsy of the wound site . Wounds in wet, moist, and dry environments were completely epithelialized on days 6, 7, and 8, respectively . Thickness of the epidermis in wet, moist, and dry wounds was 204 +/- 23, 141 +/- 12, and 129 +/- 18 (mean +/- SEM), respectively . Moist wounds had more subepidermal inflammatory cells than wet wounds . In comparison to dry wounds, the moist or the wet healing environment resulted in less necrosis and faster and better quality of healing in the formation of the newly regenerated epidermis.

Acta Med Port, 1995 May, 8(5), 313 - 7
{Neurosyphilis and AIDS}; Quaresma MJ et al.; Syphilis in HIV-infected patients reveals some particular aspects which are clinically relevant and disturbing: it is more frequent and develops more quickly to late stages, namely neurosyphilis; this progression may happen even if classic therapy in the early stages has been undertaken; the diagnosis of neurosyphilis is rather complex, the serological tests being of no definite credit; high doses of intravenous penicillin should be administered for a long period . We report a case that exemplifies the aspects described above.

Biotechnol Prog, 1995 May-Jun, 11(3), 299 - 305
Metabolic control analysis of the penicillin biosynthetic pathway in a high-yielding strain of Penicillium chrysogenum; Nielsen J et al.; Metabolic control analysis is used to identify the rate-limiting step in the penicillin biosynthetic pathway in Penicillium chrysogenum . The analysis is carried out using a kinetic model for the first two steps in the pathway, i.e., the ACV synthetase (ACVS) and the isopenicillin N synthetase (IPNS) . The kinetic model is based on Michaelis-Menten type kinetics, with noncompetitive inhibition of the ACVS by ACV and competitive inhibition of the IPNS by glutathione . From measurements of the enzyme activities and intracellular metabolites during a fed-batch cultivation, the kinetic model is used to predict the flux through the pathway . The model prediction corresponds well with the measured rate of penicillin biosynthesis . From measurement of the activity of the acyl-CoA:isopenicillin acyltransferase, which catalyzes the third and last reaction in the pathway, it is concluded that the rate-limiting step is either at the ACVS or at the IPNS . From the kinetic model, the elasticity coefficients and the flux control coefficients are calculated throughout the fed-batch cultivations, and it is found that there is a shift in the flux control from the ACVS to the IPNS during the cultivation.

Reprod Toxicol, 1995 May-Jun, 9(3), 275 - 80
Interlaboratory evaluation of embryotoxicity in the postimplantation rat embryo culture; Piersma AH et al.; The embryotoxicity of eight xenobiotic compounds in rat postimplantation whole embryo culture was blindly tested in four laboratories according to a standard protocol . The results show that the four nonteratogens amaranth, penicillin, isoniazid, and saccharin did not affect embryogenesis apart from general toxicity at very high concentrations in culture for amaranth and isoniazid . There was good concordance of results across the laboratories . The four teratogens (retinoic acid, 6-aminonicotinamide, acetylsalicylic acid, and vincristine) induced a variety of specific embryotoxic effects, which were in most cases similar in all laboratories . These results indicate that the definition for specific embryotoxicity used, as well as the culture duration and embryonic age are crucial for concordant scoring . Other methodologic differences did not significantly influence scoring of embryotoxicity . Therefore, within the limits of the end points and embryonic stage represented in the method, embryo culture appears as a useful method for embryotoxicity screening, which can be reproducibly applied in different laboratories.

Hear Res, 1995 May, 85(1-2), 122 - 6
Cochlear effects of indacrinone are not altered by penicillin; Rybak LP et al.; Indacrinone is a loop diuretic structurally related to ethacrynic acid . Indacrinone is a racemic mixture . Previous studies have shown that the (-) enantiomer caused reduction of endocochlear potential (EP) and elevation of compound action potential (CAP) threshold (Rybak and Whitworth, 1987a) . It has been demonstrated that organic acids such as penicillin, probenecid and sodium salicylate prevent the reduction of EP normally observed after furosemide administration (Rybak et al., 1992a) . The present study was designed to determine whether penicillin pretreatment could prevent changes in EP and CAP threshold in (-)-indacrinone treated chinchillas . Adult chinchillas were anesthetized with ketamine and pentobarbital . A microelectrode was advanced into the scala media using the round window approach, and CAP responses to clicks were measured . One group was treated with (-)-indacrinone 100 mg/kg via the jugular vein . A second group of animals received penicillin 50 mg/kg i.v . thirty minutes before (-)-indacrinone . The mean EP change in the indacrinone-treated animals was 38.38 +/- 19.32 millivolts (mv) . The reduction of EP in the group receiving penicillin was 24.43 +/- 20.74 mv (P > 0.09) . The mean CAP threshold changes in animals receiving indacrinone was 20 +/- 14.14 dB whereas those pretreated with penicillin showed a threshold shift of 21.43 +/- 20.35 dB (P > 0.05) . These findings are consistent with previous studies which showed that the effect of ethacrynic acid on the EP and CAP was not changed by the pretreatment with penicillin (Rybak et al., 1990).

Biokhimiia, 1995 May, 60(5), 791 - 7
{Penicillin acylase from Escherichia coli: catalytically active subunits}; Kabakov VE et al.; Gel filtration under denaturing conditions was used to isolate the alpha- and beta-subunits of penicillin acylase (PA) . Refolded subunits were obtained through removing urea by dialysis . Both renatured subunits were catalytically active during hydrolysis of phenylacetic acid p-nitroanilide; this activity decreased after addition of a serine-specific inhibitor--phenylmethanesulfonyl fluoride . The subunits were also active in reversed micelles of Aerosol OT (AOT) in octane, the optimum hydration degree being 11.9 and 17.5 for the light (alpha) and heavy (beta) subunits, respectively . The positions of the maxima were consistent with both theoretically calculated optimum hydration degrees and the earlier reported profile of enzymatic activity for native PA in reversed micelles.

Am J Med, 1995 Apr 24, 98(4A), 52S - 56S; discussion 56S-59S
Neuroborreliosis; Halperin JJ; Lyme disease is a multisystem infectious disease with frequent nervous system involvement . It affects peripheral nerves, the meningeal lining of the central nervous system (CNS), and the CNS parenchyma, but the underlying pathophysiology remains unclear . Considerable data suggest that dividing Lyme neuroborreliosis into early and late disease stages, as has been done with syphilis--the other well-known spirochetosis that affects the nervous system--lacks pathophysiologic validity . Early CNS seeding has been demonstrated, however, and lymphocytic meningitis and facial paralysis tend to occur relatively early in infection, although radiculoneuropathy and cranial neuropathies may also occur later . Less fulminant forms of peripheral nerve or CNS involvement may present later in the disease course . Encephalomyelitis may occur early or late but is rare; encephalopathy is far more common and tends to occur in patients with evidence of systemic (but not necessarily CNS) Lyme disease . Diagnosis of CNS infection has been difficult, and most studies have relied on indirect methods . Demonstration of intrathecal production of anti-Borrelia burgdorferi antibodies provides the strongest evidence, but correction for the amount of peripheral blood immunoreactivity to B . burgdorferi that crosses the blood-brain barrier is essential . Newer technologies have been applied in an effort to improve detection of B . burgdorferi itself--polymerase chain reaction may provide a sensitive tool for organism detection to complement immunologic techniques . The optimal treatment regimen for Lyme disease has not been defined, but a course of ceftriaxone (2 g/day) or cefotaxime (6 g/day) for 3-4 weeks is commonly prescribed . Intravenous penicillin and oral doxycycline (200 mg/day) for 2 weeks have been used successfully to treat Lyme meningitis, but these results require confirmation.

Biochem J, 1995 Apr 15, 307 ( Pt 2), 335 - 9
Streptomyces K15 active-site serine DD-transpeptidase: specificity profile for peptide, thiol ester and ester carbonyl donors and pathways of the transfer reactions; Grandchamps J et al.; The Streptomyces K15 transferase is a penicillin-binding protein presumed to be involved in bacterial wall peptidoglycan crosslinking . It catalyses cleavage of the peptide, thiol ester or ester bond of carbonyl donors Z-R1-CONH-CHR2-COX-CHR3-COO- (where X is NH, S or O) and transfers the electrophilic group Z-R1-CONH-CHR2-CO to amino acceptors via an acyl-enzyme intermediate . Kinetic data suggest that the amino acceptor behaves as a simple alternative nucleophile at the level of the acyl-enzyme in the case of thiol ester and ester donors, and that it binds to the enzyme.carbonyl donor Michaelis complex and influences the rate of enzyme acylation by the carbonyl donor in the case of amide donors . Depending on the nature of the scissile bond, the enzyme has different requirements for substituents at positions R1, R2 and R3.

Blood, 1995 Apr 15, 85(8), 2238 - 44
Functional asplenia in hemoglobin SC disease; Lane PA et al.; The incidence of functional asplenia in sickle-hemoglobin C (SC) disease has not been defined, and the use of prophylactic penicillin to prevent life-threatening septicemia in this disorder is controversial . The percentage of red blood cells with pits (pit count) is a reliable assay of splenic function in other disorders but has not been validated in hemoglobin SC disease . To address these issues, we conducted a prospective, multicenter study of splenic function in persons with hemoglobin SC disease . Baseline clinical data were recorded, and red blood cell pit counts were performed on 201 subjects, aged 6 months to 90 years, with hemoglobin SC; 43 subjects underwent radionuclide liver-spleen scanning . Pit counts greater than 20% were associated with functional asplenia as assessed by liver-spleen scan, whereas pit counts less than 20% were found in subjects with preserved splenic function . Pit counts greater than 20% were present in 0 of 59 subjects (0%) less than 4 years of age, in 19 of 86 subjects (22%) 4 to 12 years of age, and in 25 of 56 subjects (45%) greater than 12 years of age . Other subjects with hemoglobin SC, who had previously undergone surgical splenectomy, had higher pit counts (59.7% +/- 9.5%) than splenectomized subjects without hemoglobinopathy (38.5% +/- 8.8%) or with sickle cell anemia (20.5% +/- 1.9%; P < .001) . Two subjects with hemoglobin SC disease (not splenectomized), ages 14 and 15 years, with pit counts of 40.3% and 41.7% died from pneumococcal septicemia . These data indicate that functional asplenia occurs in many patients with hemoglobin SC disease, but its development is usually delayed until after 4 years of age . The pit count is a reliable measure of splenic function in hemoglobin SC disease, but values indicative of functional asplenia (> 20% in our laboratory) are higher than in other disorders . The routine administration of prophylactic penicillin to infants and young children with hemoglobin SC disease may not be necessary.

Anticancer Drugs, 1995 Apr, 6(2), 324 - 6
Platin salts-induced hemolytic anemia: cisplatin- and the first case of carboplatin-induced hemolysis; Maloisel F et al.; Anemia is a common side effect of cisplatin, especially after repeated infusions . The primary mechanisms is a myelosuppression caused by cisplatin's interference with iron metabolism, resulting in a lower count of red cell precursors . Some authors report a hemolytic anemia similar to penicillin-induced anemia, in which hemolysis is caused by an antiglobulin antibody directed against red cell membrane-bound cisplatin . The authors report two cases of cisplatin-induced anemia and suggest that the immune-complex hypothesis is responsible for hemolysis . The first case of carboplatin-induced hemolysis is also reported . Mechanisms of hemolysis and clinical practice are discussed.

Sangre (Barc), 1995 Apr, 40(2), 115 - 9
{Treatment with fludarabine of chronic refractory lymphoid leukemia}; Herrero M et al.; PURPOSE: New antimetabolic drugs, purine-analogous, have been introduced in the treatment of advanced or refractory cases of chronic lymphocytic leukaemia (CLL), fludarabine (FLU) being one of such drugs . The results attained with FLU in 6 cases of refractory CLL are reported . PATIENTS AND METHODS: The efficacy and toxicity of FLU was evaluated in 6 patients (median age 63 years) between March 1993 and March 1994 . Five patients were in stage III-IV and one in stage II of the Rai's system, and they were refractory to the usual treatment . The dosis used here was 30 mg/sq m/day, for 5 days every 4 weeks, up to a total of 6 therapeutic courses . The response was assessed after 3 and 6 courses . Anti-infectious prophylaxis was made with co-trimoxazole, monthly benzathine penicillin G and isoniazid in Mantoux-positive patients . The response criteria were those given by the NIC Working Group for CLL . RESULTS: The patients received 2 to 6 courses . None of them attained complete remission: 1 had nodular remission, 2 had partial remission, 2 responded partially although not reaching criteria for partial remission (1 died of pancytopenia), and 1 had disease progression and died after the second course . Fast and important reduction of the lymphocyte count as well as the CD4 lymphocytes was present in all cases . Bone-marrow infiltration decreased strikingly in 2 cases and the platelet count improved in 3 cases and worsened in 2 others . The following toxicity was recorded: 2 patients had nausea, 5 had neutropenia (below 500 x 10(9)/L in 3 instances) and 4 had thrombocytopenia (lower than 40 x 10(9)/L in one case) . In 26 therapeutic courses there were 10 febrile episodes (1 for pneumonia, 1 for gastroenteritis and 8 without any septic foci); 1 patient developed pulmonary tuberculosis after completing the treatment and one patient died of posttransfusion graft versus host disease after splenectomy once she had completes six courses . CONCLUSION: This experience confirms the efficacy of FLU in the treatment of refractory B-CLL patients and is in agreement with previous reports as no response is initiated after the 3rd course . The lymphocyte count decreases quickly and strikingly . Depletion of CD4 lymphocytes along with neutropenia and hypogammaglobulinaemia make these patients highly sensitive to all types of infection, chiefly by opportunistic germs, so adequate anti-infectious prophylaxis is of great importance . The two patients with pre-treatment haemoglobin and platelet values lower than 10 g/dL and 40 x 10(9)/L, respectively, were the only ones in need of transfusion . No cumulative myelosuppression was appreciated.

Appl Microbiol Biotechnol, 1995 Apr, 43(1), 123 - 30
Analysis of penicillin V biosynthesis during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum; Jorgensen H et al.; Metabolites (both intra- and extracellular) involved in penicillin biosynthesis were measured during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum . The fed-batch cultivations were carried out on a complex medium containing corn steep liquor . Three distinct phases were observed: (a) a rapid growth phase where free amino acids present in the medium are metabolized, (b) a linear growth phase, and (c) a stationary phase . The specific penicillin production (rp) is initially high and, during the rapid growth phase, it increases slightly . During the linear growth phase rp is approximately constant {4-6 mg penicillin V (g dry weight)-1 h-1 depending on the operating conditions}, whereas it decreases during the stationary phase . During the cultivations the tripeptide Aad-Cys-Val (the first metabolite in penicillin biosynthesis) and 8-hydroxypenillic acid (formed by carboxylation of 6-aminopenicillanic acid, 6-APA) were found to accumulate in the medium, whereas the concentrations of isopenicillin N and 6-APA were found to be approximately constant and low . About 3% of the Aad-Cys-Val formed in the first step of the penicillin biosynthetic pathway is lost to the medium and 4% of the isopenicillin N formed in the second step of the pathway is lost as extracellular isopenicillin N, 6-APA or 8-hydroxypenillic acid . Also the cyclic form of alpha-aminoadipic acid, 6-oxo-piperidine-2-carboxylic acid, was found to accumulate in the medium and it was found to be formed in an approximately constant ratio to penicillin V of 6 mol/100 mol.

Md Med J, 1995 Apr, 44(4), 284 - 8
Ocular syphilis and neurosyphilis in a patient with human immunodeficiency virus infection; Friedman RF et al.; A patient who presented with severely decreased bilateral vision was found to have syphilis and neurosyphilis that responded well to a 14-day course of penicillin and prednisone . The patient tested positive for HIV, which can alter the natural course of syphilis, often making the diagnosis and treatment difficult . Conventional therapy for syphilis may not be effective in patients with HIV . Any patient with syphilis who is in a high-risk group should be tested for HIV; conversely, any patient with HIV should be tested for syphilis if signs or suspicions exist.

J Bacteriol, 1995 Apr, 177(8), 2074 - 9
Identification and cloning of the gene encoding penicillin-binding protein 7 of Escherichia coli; Henderson TA et al.; Penicillin-binding protein (PBP) 7 of Escherichia coli is a poorly characterized member of the family of enzymes that synthesize and modify the bacterial cell wall . The approximate chromosomal position of the gene encoding this protein was determined by measuring the expression of PBPs during lytic infection of E . coli by each of the 476 miniset members of the Kohara lambda phage genomic library . Phages lambda 363 and lambda 364, encompassing the region from 47.7 to 48 min of the chromosome, overproduced PBP 7 . One open reading frame, yohB, was present on both these phages and directed the expression of PBPs 7 and 8 . The predicted amino acid sequence of PBP 7 contains the consensus motifs associated with other PBPs and has a potential site near the carboxyl terminus where proteolysis by the OmpT protein could occur, creating an appropriately sized PBP 8 . The PBP 7 gene (renamed pbpG) was interrupted by insertion of a kanamycin resistance gene cassette and was moved to the chromosome of E . coli . No obvious growth defects were observed, suggesting that PBP 7 is not essential for growth under normal laboratory conditions.

South Med J, 1995 Apr, 88(4), 392 - 6
The American Social Health Association celebrates 80 years of fighting sexually transmitted diseases; Nixon SA et al.; The American Social Health Association (ASHA) can look back on 80 years of service as the only national nongovernmental organization devoted exclusively to prevention of sexually transmitted diseases (STDs) . The valuable contributions made by physicians since the agency's founding in 1914 are noted and gratefully acknowledged . To commemorate its 80th anniversary, ASHA recently published a history that discusses the movements leading to ASHA's founding, the organization's work with the military during the World Wars, the changing face of STD control once penicillin became widely available in the 1940s, and the response to newly identified infections in recent decades . It also lists ASHA's founders, board presidents, executive directors, and recipients of the William Freeman Snow Award for outstanding contributions in the field of sexually transmitted diseases . The history was written by Kay Flaminio and David Klaassen of the ASHA Archive . This article summarizing ASHA's history was written especially for the Journal by Sam A . Nixon and Kay Flaminio . Nixon, a long-time member of the Southern Medical Association, recently retired as an associate network medical director of BlueCross BlueShield of Texas . He has maintained an interest in STD prevention and the work of the ASHA for many years, currently serving as the vice chair of ASHA's board of directors . Kay Flaminio is a member of the staff of ASHA.

J Pharmacol Exp Ther, 1995 Apr, 273(1), 146 - 53
Organic anion transport in rabbit renal basolateral membrane vesicles; Makhuli MJ et al.; Pathways for p-aminohippurate (PAH) transport across the basolateral membrane of rabbit proximal tubule cells were investigated from studies of {3H} PAH uptake in membrane vesicles isolated by Percoll-density gradient centrifugation . The 10-s uptake of PAH was not significantly different when measured in the absence of cation gradients or in the presence of inwardly directed Na, Li, K or choline gradients that suggests the absence of a mechanism mediating Na-PAH cotransport . A probenicid-sensitive, trans-stimulation of {3H} PAH uptake was observed in the presence of an outward PAH gradient . PAH gradient-driven {3H} PAH uptake was cis-inhibited by glutarate, alpha-ketoglutarate, adipate and sebacate and outward gradients of alpha-ketoglutarate trans-stimulated probenicid-sensitive PAH uptake . A concentrative accumulation of PAH was measured in the presence of an inward Na gradient and the dicarboxylates glutarate or alpha-ketoglutarate . Compared to the absence of a pH gradient, an inside alkaline pH gradient induced an increased PAH uptake both in the presence and absence of CO2/HCO3 . Inside-negative and inside-positive voltage differences were observed to stimulate and inhibit alpha-ketoglutarate gradient-driven PAH uptake, respectively . alpha-Ketoglutarate gradient-driven PAH uptake was progressively reduced in the presence of increasing penicillin concentration and an outward gradient of alpha-ketoglutarate induced an increased level of {14C} penicillin uptake . These results suggest the presence of a probenicid-sensitive organic anion exchange mechanism as a pathway for PAH and penicillin transport across the basolateral membrane of rabbit proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Gynecol Oncol, 1995 Apr, 57(1), 86 - 95
Interleukin-12-mediated tumoricidal activity of patient lymphocytes in an autologous in vitro ovarian cancer assay system; DeCesare SL et al.; This study was designed to examine if interleukin-12 (IL-12) can induce cytolytic function of lymphocytes from ovarian cancer patients against either an ovarian cancer cell line or their own autologous tumor cells . Lymphocytes were obtained from the peripheral blood or ascites of ovarian cancer patients and activated with IL-12 alone or concomitantly with interleukin 2 (IL-2) for 2 to 3 days . Activation of lymphocytes and assessment of tumoricidal function by a chromium release assay were performed directly in a standard control medium (RPMI 1640 containing 2 mM glutamine, 100 micrograms/ml streptomycin, 100 units penicillin, 5% heat-inactivated human AB serum, and 5 mM 4-(2-hydroxyethyl)-1-piperazinesulfonic acid) and in 50% ascitic fluid (50% by volume filter-sterilized ascites with 50% of the above-mentioned control medium) . Target cells were added directly into the medium in which the lymphocytes were activated in order to more closely mimic in vivo conditions . Lymphocytes, activated by IL-12 in 50% ascitic fluid, were able to lyse autologous tumor cells in 3 of 6 assays and were able to lyse SKOV3 cells (an ovarian cancer cell line) in 5 of 7 assays . The results were not significantly different in the control medium . When both IL-2 and IL-12 were used to activate lymphocytes in 50% ascitic fluid, significant cytotoxicity was generated in 6 of 6 autologous assays and in all 7 patient assays using SKOV3 as a target (P < 0.05) . Synergy between the two cytokines was seen in all 13 patient assays in ascitic medium compared to only 5 of 13 assays in control medium . Additionally, when lymphocytes were stimulated with both IL-2 and IL-12, significantly greater cytotoxicity was seen in the ascitic fluid medium compared to the control medium in 13 of 14 assays (P < 0.05) . No significant tumoricidal activity was seen by lymphocytes maintained in either medium without the addition of IL-2 or IL-12 . Ascitic fluid consistently potentiates the synergy between IL-2 and IL-12 in generating cytotoxicity against ovarian cancer cells but does not increase cytotoxicity induced by IL-12 alone . IL-12 by itself activates tumoricidal activity of lymphocytes in ascitic fluid; however, the addition of IL-2 increases the degree and consistency of this effect . These data support the possibility that IL-12 may warrant further investigation as a potential therapeutic agent in the treatment of advanced ovarian cancer.

Eur Heart J, 1995 Apr, 16 Suppl B, 90 - 3
The medical treatment of culture-negative infective endocarditis; Oakley CM; The most common cause for persistently negative blood cultures is the previous administration of antibiotics, but other causes include fastidious organisms (such as Brucella and Legionella), cell-dependent organisms (such as Chlamydia and Coxiella), fungi and a major immune reaction . Fastidious organisms may take up to 3 weeks to grow in optimal media . Abscess formation may take the organisms inaccessible . If the diagnosis is in doubt, echocardiography, and more specifically transoesophageal echocardiography, is invaluable . If the clinical diagnosis is made but cultures are unavailable or negative, treatment should be started without delay . The choice of antibiotic depends on the clinical setting . In general, penicillin and gentamicin are indicated for a subacute onset: flucloxacillin and gentamicin if the onset is acute . Intravenous drug abusers should receive vancomycin; those who have recently had a prosthetic valve inserted should receive vancomycin, together with rifampicin and gentamicin.

Eur Heart J, 1995 Apr, 16 Suppl B, 122 - 5
The prophylaxis of infective endocarditis: current practices in France . French Federation of Cardiology; Danchin N; Over the last 10 years, the French Federation of Cardiology has circulated recommendations regarding the use of chemoprophylaxis in patients at risk for infective endocarditis . A national survey conducted in 1991, however, showed that the vast majority of both general practitioners and dentists were unaware of these recommendations . Therefore, a Consensus Conference was convened in 1992, with the object of defining and circulating new guidelines which were to be as practical as possible, for the prophylaxis of infective endocarditis . The Consensus Conference first defined which categories of subjects were at risk for infective endocarditis and which types of procedures were potential causes of endocarditis . The second task of the Conference was to determine recommendations for chemoprophylaxis before procedures at risk . For ambulatory dental procedures, a single oral dose of 3 g of amoxicillin administered in the hour preceding the procedure was recommended . Additional recommendations were made for subjects with an allergy to penicillin, for procedures requiring general anaesthesia or for urologic or digestive tract procedures . These recommendations were printed on credit-card format cards and distributed to all practising cardiologists, who were encouraged to give each of their patients at risk a personal card bearing his/her name and the type of heart condition at risk . It is hoped that these measures to both simplify the prophylactic antibiotic regimen and circulate the recommendations from the Consensus Conference may reduce the incidence of this still severe disease.

Eur Heart J, 1995 Apr, 16 Suppl B, 110 - 3
Prevention of bacterial endocarditis in Germany; Gohlke-Barwolf C et al.; The goal of this study was to assess the current practice of endocarditis prophylaxis in Germany . We conducted a survey using a standardized questionnaire, which was sent to 100 hospital cardiologists, to 430 cardiologists in office practice and to 389 dentists and oral surgeons . In addition, 364 patients with valvular or congenital heart disease were interviewed in our outpatient clinic . Seventy five percent of cardiologists informed their patients by both written and oral instructions . Half recommended the use of penicillin, according to the German Society of Cardiology, while the rest followed recommendations of other societies . Sixty-three percent of patients who had undergone a procedure requiring prophylaxis against bacterial endocarditis within the year prior to the questionnaire, had actually received it . This is higher than previously reported, but is far from acceptable . The indications for prevention of endocarditis, as seen by the dentists, deviated markedly from official recommendations . Although 77% administered antibiotics themselves, in only 57% did the type of prophylaxis applied correspond to one of the available recommendations . Recommendations on the prevention of bacterial endocarditis are not well known dentists and oral surgeons who perform procedures for which it is indicated . Further patient- and physician-oriented strategies are urgently needed to improve compliance with prevention of endocarditis in Germany.

Pharmacol Toxicol, 1995 Apr, 76(4), 259 - 62
Malnutrition and pharmacokinetics of penicillin in Ethiopian children; Bolme P et al.; Penicillin was given to 104 children with different nutritional status, normal, underweight, marasmus and kwashiorkor . Penicillin was given either intravenously, intramuscularly or orally and the plasma concentration was followed at regular times after administration . There was a significantly decreased plasma clearance of penicillin in all malnourished groups compared to the normal weight-for-age group . The half-lives of penicillin were, however, not significantly different between the nutritional groups . This was explained by the fact that also the volume of distribution was decreased in the malnourished group with a net result that the half-life was unchanged . The bioavailability was decreased if penicillin was given to non-fasting individuals . The greatest difference between fasting and non-fasting was seen in the severely malnourished children with marasmus and kwashiorkor . Therefore, it is advised that, if penicillin is given orally to very sick and undernourished children, the dose should be increased and preferably be given in the fasting state.

Aliment Pharmacol Ther, 1995 Apr, 9(2), 205 - 8
A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori; Katelaris PH et al.; AIM: To compare H . pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin . BACKGROUND: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H . pylori . A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin . METHODS: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily . H . pylori eradication was assessed using the 13C urea breath test . RESULTS: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P = N.S.) . Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P = 0.01) . CONCLUSIONS: These regimens are similarly effective . However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H . pylori has been reported . This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole-based dual therapy.

Rom J Neurol Psychiatry, 1995 Apr-Jun, 33(2), 103 - 8
Amino acid content of the brain in rats focal penicillin induced epilepsy; Hategan D et al.; The initial objective of the present study was to investigate the role of excitatory and inhibitory amino acids in generalized as compared to focal epilepsy, both forms being induced by the same convulsant agent, i.e . penicillin . Our attempts to obtain in the rat the generalized epilepsy, constantly induced in cats by systemic administration of penicillin, were unsuccessful . This is probably due to the rudimentary development of the cerebral cortex in rodents as compared to the feline cortex . The tentative conclusion was drawn that the cortex is the brain structure mainly involved in the genesis of petit mal seizures . Penicillin was applied to the cortex of 40 white Wistar rats and the electrical cortical activity was registered . The concentrations of glutamate, aspartate, glycine, GABA and serine were determined in the cerebral cortex, the brain stem and the cerebellum . The same amino acids were determined in the brain of 20 controls . No significant changes in the amino acid contents were obtained in the cerebral cortex . In the brain stem the glutamate level was significantly increased while the glycine content was markedly decreased . These findings are consistent with the involvement of the brain stem structures in seizure activity.

Thromb Haemost, 1995 Apr, 73(4), 713 - 8
Cultured endothelial cells regulate platelet adhesion to their extracellular matrix by regulating its von Willebrand factor content; Wu YP et al.; Endothelial cells and their extracellular matrix formed in vitro are often used as a model for subendothelium in studies on platelet-vessel wall interaction . We have characterized the influence of culture conditions of endothelial cells on the formation of extracellular matrix and on the interaction of the matrix with platelets . Passage number, time of confluence, serum concentration and the addition of heparin, growth factors and antibiotics to the culture medium were varied and the extracellular matrices were isolated . The amount of fibronectin and von Willebrand factor present in the matrix were measured and the number of platelets adhering to these matrices after perfusion with citrated whole blood at a shear rate of 1000 s-1 was determined . A three times increase of the amount of von Willebrand factor in the matrix was found when the serum concentration was increased from 2.5% to 30% . When the passage number of the cells was increased or the period during which the cells were at confluence was extended, the amount of von Willebrand factor in the matrix was decreased up to 50% . Addition of heparin or ECGS (endothelial cell growth supplement) decreased the von Willebrand factor content in the matrix . Addition of penicillin or streptomycin to the culture medium had no influence on the amount of von Willebrand factor deposited in the matrix or secreted into the medium, however, other antibiotics such as gentamycin and neomycin decrease the amount of von Willebrand factor in the matrix . No influence on the amount of fibronectin in the matrix was found under all conditions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

J Mol Biol, 1995 Mar 24, 247(2), 149 - 53
Purification, crystallisation and preliminary X-ray analysis of penicillin binding protein 4 from Escherichia coli, a protein related to class A beta-lactamases; Thunnissen MM et al.; Crystals of the penicillin binding protein 4 (PBP4) from Escherichia coli have been obtained at 37 degrees C from liquid to liquid diffusion experiments in capillaries . PBP4 was dissolved in a 1.0 M ammonium sulphate solution, buffered at pH 7.2, to a concentration of 5 mg/ml, and was layered on top of a 1.6 to 2.2 M ammonium sulphate solution . Crystals appeared within four to six weeks . They belong to space group C222 with cell dimensions a = 68.5 A, b = 100.5 A and c = 137.0 A, and diffract to at least 2.8 A resolution . There is one molecule with a molecule mass of 49,568 Da in the asymmetric unit.

Rev Prat, 1995 Mar 15, 45(6), 695 - 9
{Physician-patient relationship in human immunodeficiency virus infection}; Bryn A et al.; Since the middle of this century--with, among other, the discoveries of penicillin and of streptomycin--doctors have tended to consider themselves as powerfully armed against transmissible diseases that caused so many premature deaths . The surge of human immunodeficiency virus (HIV) has bluntly faced us with a situation we have not been prepared for, but that was the daily duty of our predecessors: to care for an epidemic disease, yet without the ability to cure it; to treat infection until it provokes death unavoidably . In the face of this renewed challenge we must reconstruct forgotten relationships that we have not learnt, and that we must adapt to the circumstances of our time and to the peculiar modes of HIV transmission . This daily facet of HIV infection is not the least . It is presented here through the testimonies of a general practitioner and a psychiatrist, with the hope that any doctor will find them thoughtful and helpful.

Am J Ophthalmol, 1995 Mar, 119(3), 372 - 4
Macular pseudohypopyon from secondary syphilis; Ouano DP et al.; PURPOSE/METHODS: Acute syphilitic posterior placoid chorioretinitis causes visual loss in patients with secondary syphilis . The condition is characterized by vitreitis and large, yellow placoid lesions in the macula . We examined a patient with syphilis who had a serious retinal detachment and an exudative fluid meniscus (pseudohypopyon) . RESULTS/CONCLUSIONS: Visual recovery and complete resolution of the chorioretinal lesion occurred after intravenous penicillin therapy . Secondary syphilis should be considered in the differential diagnosis of any patient with a macular pseudohypopyon.

Anal Chem, 1995 Mar 1, 67(5), 936 - 44
Bilayer lipid membranes for flow injection monitoring of acetylcholine, urea, and penicillin; Nikolelis DP et al.; This work describes a technique for the rapid and sensitive determination of acetylcholine, urea, and penicillin in flowing solution streams using stabilized systems of solventless bilayer lipid membranes (BLMs) . This method of monitoring substrates of hydrolytic enzyme reactions made use of BLMs which were supported on ultrafiltration membranes such as polycarbonate and glass microfiber; these filter membranes were found to enhance the stability of BLMs for uses in flow injection experiments . The enzymes were immobilized on BLMs by incorporating the protein solution into the lipid matrix at the air/electrolyte interface before the BLM formation, followed by injections of the substrates into flowing streams of a carrier electrolyte solution . Hydronium ions produced by the enzymatic reaction at the BLM surface caused dynamic alterations of the electrostatic fields and phase structure of BLMs, and as a result ion current transients were obtained; the magnitude of these signals was correlated to the substrate concentration, which could be determined at the micromolar level . The response times were ca . 10 s, and acetylcholine, urea, and penicillin could be determined in continuous flowing systems with a maximum rate of 220 samples/h . It is expected that this analytical utility of stabilized BLMs for flow stream uses will provide new opportunities in this strategy of chemical sensing.

Int J Lepr Other Mycobact Dis, 1995 Mar, 63(1), 28 - 34
Optimal pH for preserving the activity of Mycobacterium leprae during incubation of cells in a cell-free liquid medium; Nakamura M; The effect of the pH of a cell-free liquid medium on the activity of Mycobacterium leprae during incubation of the cells was investigated . As a parameter for evaluating the activity, the amount of adenosine triphosphate (ATP) extracted from the incubated cells collected by centrifugation was measured . The results demonstrate that the activity of M . leprae cells was maintained at a significant level for approximately 4 weeks at 30 degrees C in 0.05 M phosphate buffer containing 10% fetal calf serum at pH 7.0 compared to cells at other pHs tested, but activity was not preserved in phosphate buffer at pH 7.0 without serum and incubated at 37 degrees C . The maintenance of the activity under these conditions was prolonged somewhat by the addition of glycerin (2%) to the medium, and was definitely inhibited by rifampin but not by either penicillin or isoniazid . From the results reported here, it could be postulated that the optimal pH of cell-free media for the study of cultivation of M . leprae is 7.0.

Mol Immunol, 1995 Mar, 32(4), 259 - 66
Non-specific cross-reactivity of hydrophobic serum IgE to hydrophobic drugs; Gueant JL et al.; The purpose of this work was to study the involvement of serum hydrophobic IgE in non-specific cross-reactions with hydrophobic drugs such as cyclohexenyl derivatives . Hydrophobic IgE were detected by radioimmunoassay . The results were expressed as the percentage of labelled anti-IgE which were adsorbed to the drug solid phase via IgE of the patient serum . Phenyl-Sepharose IgE-RIA was at 4.6 +/- 0.7%, 125 +/- 6.5% and 17.8 +/- 8.9% in control subjects (n = 24), in atopic patients with positive Phadiatop (n = 30) and in patients with drug allergy (n = 23), respectively . We selected five patients who were allergic to either penicillin, propofol, glafenin or paracetamol and who had a Phenyl-Sepharose IgE-RIA greater than 20% . In these five cases, IgE-RIA were positive (percentage at least twice more than that obtained with control sera) with all the solid phases prepared with hydrophobic drugs such as penicillin, propofol, glafenin, paracetamol and mexiletine . Inhibition of IgE binding by monoethylene-glycol showed that the cross-reactivity was due to hydrophobic binding of IgE to the drug . Three of the five patients were allergic to penicillin and underwent on adverse reaction against another cyclohexenyl derivative, namely propofol and glafenin . In conclusion, we have observed the presence of 'hydrophobic IgE (with positive Phenyl-Sepharose RIA)' in 64% of patients allergic to a hydrophobic drug.

Curr Genet, 1995 Mar, 27(4), 351 - 8
Nuclear DNA-binding proteins which recognize the intergenic control region of penicillin biosynthetic genes; Feng B et al.; The biosynthesis of penicillin, a secondary metabolite produced by Penicillium chrysogenum, is subject to sophisticated genetic and metabolic regulation . The structural genes, pcbC and pcbAB, which encode two of the penicillin biosynthetic enzymes are separated by a 1.16-kb intergenic region and transcribed divergently from one another . To identify and characterize nuclear proteins which interact with the pcbAB-pcbC intergenic promoter region, crude and partially purified nuclear extracts were used in mobility shift and DNA footprinting assays . Multiple DNA-binding proteins appear to bind to different regions of this DNA segment . An abundant nuclear protein, nuclear factor A (NF-A), binds at a single site in the intergenic promoter region and recognizes an 8-bp sequence, GCCAAGCC . Penicillin production is sensitive to nitrogen catabolite repression . The global-acting nitrogen regulatory protein NIT2 of Neurospora crassa binds strongly to the intergenic promoter region of the pcbAB and pcbC genes at a single site that contains two closely spaced GATA sequences.

Biochim Biophys Acta, 1995 Feb 22, 1247(1), 113 - 20
Complementary roles of mutations at positions 69 and 242 in a class A beta-lactamase; Bonomo RA et al.; Analysis of the three-dimensional structure of class A beta-lactamases suggests that deformation of the substrate binding site can be produced by changes in the hydrophobicity of residue 69 behind the beta-sheet and by outward movement of the B3 beta-strand by introduction of a non-glycine residue at position 242 on the B4 beta-strand . By site-directed mutagenesis Met69-IleGly242-Cys, a double mutant, of the OHIO-1 beta-lactamase, was constructed . The minimum inhibitory concentrations (MICs) of the double mutant compared with the wild type and each single mutant revealed an increased susceptibility to beta-lactams . Met69-IleGly242Cys hydrolyzed cephaloridine (Km = 213 microM) but had Km > 500 microM for other beta-lactams tested including cefotaxime, and demonstrated a higher apparent Ki for inhibitors (clavulanate Ki = 500 microM sulbactam = 434 microM, and tazobactam = 70 microM) . In a competition experiment with cephaloridine, the apparent Ki values for penicillin and cefotaxime remained low, 21 microM and 0.7 microM, respectively . Since Ile is twice as hydrophobic as Met, the Met69-Ile mutation may result in partial collapse of the oxyanion hole . This would also increase the distance between Arg-244 and the carboxyl of clavulanic acid . The Gly242-Cys mutation opens the lower portion of the active site to bulky R groups of cephalosporins . Although these two mutations result in a catalytically impaired enzyme, they can be used to model the complementary role of two distinct residues, neither of which interacts directly with beta-lactam substrates or inhibitors.

Ugeskr Laeger . 1995 Feb 13;157(7):901.
{Pseudotumor cerebri caused by Lyme borreliosis}; Ellermann A et al.; Lyme borreliosis may cause a wide range of clinical symptoms . The two previously described paediatric cases of Lyme borreliosis with symptoms of pseudotumor cerebri were associated with characteristic cutaneous symptoms . A case of seven year-old girl with six weeks of headache, vomiting nausea and fatigue as the only symptoms was shown to suffer from pseudotumor cerebri with papilloedema and increased intracranial pressure caused Borrelia burgdorferi . Specific treatment with intravenous penicillin and later intravenous ceftriaxone (due to development of penicillin allergy) for a total of ten days caused the symptoms to gradually disappear over following three to four weeks . Hence, even if pseudotumor cerebri is the only symptom, it is recommended that testing for Lyme borreliosis should be carried out.

Hindustan Antibiot Bull, 1995 Feb-Nov, 37(1-4), 9 - 15
Purification and characterization of extracellular penicillin V acylase from Fusarium sp . SKF 235; Sudhakaran VK et al.; Penicillin V acylase from Fusarium sp . SKF 235 culture filtrate was purified to homogeneity . The enzyme was a glycoprotein and composed of single polypeptide chain with molecular weight of 83,200 Daltons . The pH and temperature optima were 6.5 and 55 degrees C, respectively . The KM for penicillin V was 10 mM but the enzyme was inhibited by penicillin V at concentrations above 50 mM . Products of reaction, 6-aminopenicillanic acid and phenoxyacetic acid inhibited the enzyme competitively and noncompetitively with Ki values of 18 mM and 45 mM, respectively . The enzyme specifically hydrolyzed penicillin V, cephalosporanic acid V and penicillin V sulphoxide . Other phenoxy acetyl amides studied were not hydrolysed . It is proposed that phenoxyacetyl moiety alone is not recognized by the penicillin V acylase and in addition, the beta-lactam structure contributes in formation of enzyme-substrate complex.

FEMS Microbiol Lett, 1995 Feb 1, 126(1), 63 - 7
Carbon regulation of penicillin biosynthesis in Aspergillus nidulans: a minor effect of mutations in creB and creC; Espeso EA et al.; Transcription of the Aspergillus nidulans ipnA gene is under carbon regulation . Loss-of-function mutations in creB or creC do not cause full derepression of ipnA transcript levels in sucrose-grown mycelia and do not elevate repressed penicillin levels, indicating that neither of these genes plays a major regulatory role in penicillin biosynthesis . However, these mutations reduce external pH acidification, accelerate sucrose degradation and result in extracellular accumulation of resulting D-glucose and D-fructose . These effects would explain the partial elevation of carbon-repressed ipnA transcript levels observed in strains carrying creB- or creC- mutations.

J Bacteriol, 1995 Feb, 177(4), 992 - 7
Beta-lactam-induced bacteriolysis of amino acid-deprived Escherichia coli is dependent on phospholipid synthesis; Rodionov DG et al.; The penicillin tolerance of amino acid-deprived relA+ Escherichia coli is attributed to the stringent response; i.e., relaxation of the stringent response suppresses penicillin tolerance . The beta-lactam-induced lysis of amino acid-deprived bacteria resulting from relaxation of the stringent response was inhibited by cerulenin, or by glycerol deprivation in the case of a gpsA mutant (defective in the biosynthetic sn-glycerol 3-phosphate dehydrogenase) . Therefore, beta-lactam-induced lysis of amino acid-deprived cells was dependent on phospholipid synthesis . The lysis process during amino acid deprivation can be experimentally dissociated into two stages designated the priming stage (during which the interaction between the beta-lactam and the penicillin-binding proteins occurs) and the beta-lactam-independent lysis induction stage . Both stages were shown to require phospholipid synthesis . It has been known for some time that the inhibition of phospholipid synthesis is among the plethora of physiological changes resulting from the stringent response . These results indicate that the inhibition of peptidoglycan synthesis and the penicillin tolerance associated with the stringent response are both secondary consequences of the inhibition of phospholipid synthesis.

J Am Acad Dermatol, 1995 Feb, 32(2 Pt 1), 255 - 61
From mercury to malaria to penicillin: the history of the treatment of syphilis at the Mayo Clinic--1916-1955; Sartin JS et al.; Between 1916 and 1955 the Mayo Clinic became recognized as one of the premier institutions specializing in the treatment of syphilis . First under the direction of John H . Stokes (1916-1924) and later Paul A . O'Leary (1924-1953), its Department of Dermatology and Syphilology, together with the members of the Clinical Cooperative Study Group, oversaw the establishment of standardized methods for the administration of the existing arsenicals and the introduction of new therapies . Malaria therapy, heat therapy, penicillin, and oxytetracycline each represented important advances in the treatment of syphilis and were extensively evaluated . Two important ancillary benefits of syphilis treatment were the development of routine intravenous techniques, which would later prove invaluable for the administration of antibiotics and cancer drugs, and the establishment of large cooperative clinical trials, the first of their kind . Under the leadership of Stokes and O'Leary the department produced a stream of pivotal clinical research that contributed to the effective management of syphilis in the United States.

Eur J Neurosci, 1995 Feb 1, 7(2), 192 - 7
Regional hypometabolism in an acute model of focal epileptic activity in the rat; Bruehl C et al.; Focal epileptic activity can be expected to influence distant brain areas via far reaching connections . To investigate such interactions the effects of focal epileptic activity on the metabolism of the brain were investigated in the rat cortex . Focal epileptic activity was induced by the application of penicillin onto the motor cortex . The focus, and to a lesser extent homotopic contralateral brain areas, showed an increase in the regional cerebral metabolic rate of glucose (rCMRGlc) as measured by {14C}deoxyglucose autoradiography . This focal hypermetabolism was accompanied by widespread hypometabolism lateral to the focus . The decrease of rCMRGlc occurred in somatosensory cortical areas but not in the motor cortex behind or in front of the focus, the perirhinal cortex or the occipital cortex . It was associated with an increase in metabolic rate in the ventrolateral, ventroposteromedial, ventroposterolateral and, in particular, posterior nuclei of the thalamus . It is hypothesized that the widespread reduction of rCMRGlc in the somatosensory cortical areas is due to inhibition via thalamic nuclei caused by activity in the motor cortex.

J Clin Microbiol, 1995 Feb, 33(2), 371 - 5
Effects of select medium supplements on in vitro development of Cryptosporidium parvum in HCT-8 cells; Upton SJ et al.; Surface-sterilized oocysts of Cryptosporidium parvum were applied to subconfluent monolayers of human adenocarcinoma (HCT-8) cells grown on coverslips in six-well cluster plates . Parasite-infected cultures were then incubated in RPMI 1640 with 10% fetal bovine serum, 15 mM HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffer, and antibiotics at 37 degrees C in a 5% CO2-95% air incubator for 2 h to allow sporozoites to excyst and enter cells . After cultures were washed free of debris, fresh cell culture media containing select supplements were added and cultures were reincubated . Parasite growth was assessed 66 h later by counting the number of parasite developmental stages in 25 random x 100 oil fields by Nomarski interference-contrast microscopy . Four vitamin supplements, calcium pantothenate, L-ascorbic acid, folic acid, and 4-(para)-aminobenzoic acid, each resulted in a significant increase in parasite numbers in vitro . The addition of insulin and the sugars glucose, galactose, and maltose also had a positive effect on parasite growth, although the effect was less pronounced than with any of the vitamins . Using the above information, we developed a supplemental medium formulation consisting of RPMI 1640 with 10% fetal bovine serum, 15 mM HEPES, 50 mM glucose, and 35 micrograms of ascorbic acid, 1.0 micrograms of folic acid, 4.0 micrograms of 4-aminobenzoic acid, 2.0 micrograms of calcium pantothenate, 0.1 U of insulin, 100 U of penicillin G, 100 micrograms of streptomycin, and 0.25 microgram of amphotericin B (Fungizone) per ml (pH 7.4) . The growth of c . parvum in this medium was found to be enhanced approximately 10-fold compared with that in control medium without additional glucose, insulin, or vitamins.

Ear Nose Throat J, 1995 Feb, 74(2), 114 - 7
Eikenella corrodens: an unexpected pathogen causing a persistent peritonsillar abscess; Knudsen TD et al.; Eikenella corrodens is a known pathogen in head and neck infections, especially in wounds related to oral cavity contamination . It is uniformly resistant to clindamycin . It is frequently an indolent infectious process, and patients often have persistent or recurrent symptoms despite several weeks of what many would feel would be appropriate antibiotic therapy . A high index of suspicion is necessary to make the correct diagnosis, and culture and sensitivity results are paramount to confirm the diagnosis . Appropriate antibiotic therapy with penicillin, ampicillin, select cephalosporins, to the augumented penicillins is the treatment of choice in most cases, with surgical drainage of abscess cavities and/or debridement of nonviable tissue reserved for appropriate cases and indications.

Biochem Mol Biol Int, 1995 Feb, 35(2), 441 - 6
Revealing active site on the light subunit of penicillin acylase; Kabakov VE et al.; Serine-specific irreversible inhibitor phenylmethanesulfonyl fluoride (PMSF) inactivates penicillin acylase subunits, which were chromatographically separated under denaturing conditions and refolded by dialysis, in aqueous solution and Aerosol OT reversed micelles . The activities of both alpha and beta subunits decrease with increasing PMSF concentration but the dependence is no longer linear, in contrast with the native enzyme . The enzyme inactivated in aqueous solution, when solubilized in the micellar system at Wo = 12, exhibits an additional activity, which can be further inhibited by PMSF.

Ital J Neurol Sci, 1995 Feb-Mar, 16(1-2), 79 - 82
Feline generalized penicillin epilepsy; Avoli M; Feline generalized penicillin epilepsy represents an experimental model of generalized spike-and-wave discharges occurring during clinical absence attacks . Spike-and-wave discharges of feline generalized penicillin epilepsy also have a pharmacological profile that is similar to that encountered in human absence attacks . Studies on the respective roles played by the thalamus and cortex in the generation of spike-and-wave discharges indicate that both structures are important in the elaboration of such generalized activity . Moreover, GABAA-mediated, intracortical inhibitory mechanisms are preserved and eventually enhanced at a time when generalized spike-and-wave discharges of feline generalized penicillin epilepsy are recorded . A preservation of GABA-mediated mechanisms in pure absence epilepsy might explain the differences in prognostic outlook that characterizes this type of epilepsy from seizures in which GABAergic mechanisms break down (e.g., generalized convulsive and partial epileptic attacks).

Allergy, 1995 Feb, 50(2), 113 - 8
Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes; Romano A et al.; We assessed 195 subjects with histories of adverse reactions to aminopenicillins, using 1) skin tests with penicilloyl polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), amoxicillin, and ampicillin (read after 20 min and 48 h); 2) patch tests with PG, amoxicillin, and ampicillin; and 3) RAST for penicilloyls G and V . Oral challenges with ampicillin, amoxicillin, and penicillin V were administered to 34/60 patients reporting maculopapular reactions . Immediate hypersensitivity (IH), in most cases for both penicillin and aminopenicillins, was diagnosed (based on skin tests, RAST, or both) in 35 subjects who had suffered anaphylactic shock, or urticaria, angioedema, or both urticaria and angioedema . Thirty-three of the 60 subjects reporting maculopapular reactions presented delayed intradermal and patch-test positivity, indicating delayed hypersensitivity (DH), for ampicillin and amoxicillin, and three were also positive for PG . Diagnoses were confirmed with oral challenges in 18/33 . The remaining 27/60 were negative in all allergologic tests, with oral-challenge confirmation in 16 . Our findings highlight the importance of the amino group in DH to aminopenicillins . Moreover, the mean time interval between the last reaction and our tests was significantly (P < 0.01) longer in DH subjects (54.96 months) than in those with IH (18.62 months), suggesting that the time of testing is less important in cases of DH.

Biochem Biophys Res Commun, 1995 Jan 17, 206(2), 629 - 36
New insights on the specificity of penicillin acylase; Roa A et al.; In contrast with the general thought that penicillin G acylases (PGAs) were only able to hydrolyse amides or esters of higly hydrophobic acids, we have demonstrated that the PGA from Kluyvera citrophila catalysed the hydrolysis of 4-nitrophenyl esters of acetic, propionic, butyric and valeric acids . Values of kcat . and kcat./Km were greatest for the first compound and less than values for benzylpenicillin by factors of 30 and 7, respectively . 4-Nitrophenyl acetate was hydrolysed faster than 2-nitrophenyl acetate but slower than phenyl acetate . The pH dependence of the reaction was similar to that of benzylpenicillin . Several experiments showed that hydrolysis of 4-nitrophenyl acetate was not catalysed by contaminating esterase activity . The implications for the structural basis of substrate binding are discussed . These substrates open, for the first time, a way to investigate the kinetic parameters of PGA at the presteady-state and provides a new perspective about the role of PGA in nature.

Ugeskr Laeger, 1995 Jan 9, 157(2), 157 - 61
{Leptospirosis in the Ribe County 1980-1991}; Biegel E et al.; Though only 4.2% of the Danish population live in Ribe County, 12 cases of leptospirosis (22% of the Danish total) were found in the county between 1980-1991 . Nine cases were associated with fresh water angling or fish farming . The patients were typically young or middle-aged formerly healthy men, who suddenly became ill with acute febrile disease . Eleven patients survived, one died . Cases were most often seen in late summer and autumn . Four patients required dialysis, and these patients also had relatively high serum levels of bilirubin . Case history and simple laboratory findings are helpful in leading to the diagnosis . Three patients were admitted with the correct diagnosis, and by the third day in hospital all 12 were being treated with relevant antibiotics, eight on suspicion of leptospirosis . Three patients had positive blood cultures on day 4, 6 and 9, and nine patients had late positive serology, two of whom also belonged to the group with positive blood cultures . In two patients the diagnosis was based on clinical findings alone . For these reasons, penicillin should be commenced on clinical suspicion alone.

Mol Gen Genet, 1995 Jan 6, 246(1), 110 - 8
Overexpression of two penicillin structural genes in Aspergillus nidulans; Fernandez-Canon JM et al.; We have placed two different penicillin structural genes from Aspergillus nidulans, ipnA (encoding isopenicillin N synthetase, IPNS) and acyA (encoding acyl-CoA:6-aminopenicillanic acid acyltransferase, AAT), under the control of the strong alcA promoter {alcA(p)} . Single copies of these transcriptional fusions were targeted to the same chromosomal location and conditions have been worked out which simultaneously allow induction of the alcA(p) and support penicillin biosynthesis . Transcriptional induction of the chimeric genes alcA(p)::ipnA or alcA(p)::acyA(cdna) in the relevant recombinant strains results in 10-fold higher levels of the ipnA or acyA transcripts than those resulting from transcription of the corresponding endogenous genes . This increase causes a 40-fold rise in IPNS activity or a 8-fold rise in AAT activity . Despite this rise in enzyme levels, forced expression of the ipnA gene results in only a modest increase in levels of exported penicillin, whereas forced expression of the acyA gene reduces penicillin production, showing that neither of these enzymes is rate-limiting for penicillin biosynthesis in A . nidulans . A genomic version of the alcA(p)::acyA fusion in which the acyA gene is interrupted by three small introns, is inducible by threonine to a lesser extent (as determined by both acyA mRNA levels and AAT enzyme levels) than the corresponding cDNA version, suggesting that processing of the introns present in the primary transcript may limit acyA expression.

Chin J Biotechnol, 1995, 11(4), 259 - 66
Modeling of penicillin G hydrolysis to 6-APA in an immobilized enzyme-ion exchange system; Chen J et al.; A composite system of an immobilized enzyme reactor combined with an ion exchange column was employed for hydrolysis of penicillin G to 6-APA with continuous removal of PAA . In this study, a mathematical model of penicillin G hydrolysis to 6-APA in the composite system was developed based on the compartment model, the profile of concentration in the ion exchange column, and the enzyme kinetics in the immobilized enzyme reactor . After checking the simulation values and experimental data, the effects of the resin volume, the flow rate, and the switching time on the time required to reach the desired conversion rate was also examined by computer simulation.

Medicina (B Aires), 1995, 55(4), 337 - 40
{Primary bronchial actinomycosis and foreign body}; Mingrone H et al.; This paper presents the fourth case reported on the association of primary bronchial actinomycosis and foreign body . The pathogenesis of this rare association has been linked to the low respiratory tract and a foreign body (chicken bone); it depends on its characteristics and how long it has remained lodged into the bronchial tree . The diagnosis of this case was very difficult and late . Several endoscopy procedures were required in order to detect it . Our patient has been treated successfully with parenteral penicillin in association with an original bronchoscopic procedure using a laser technique to find the foreign body and take it out of the respiratory tract . We consider that it is necessary to remember this association in every patient who suffers from recurrent pneumonia, in those who are at risk of foreign body aspiration and when the presence of an endobronchial mass is suspected.

Acta Neurobiol Exp (Wars), 1995, 55(4), 281 - 7
Effects of repeated systemic penicillin injections on nonconvulsive and convulsive epileptic seizures in the rat; Stankiewicz J et al.; Changes in the spontaneous and induced epileptic activity in the course of repetitive systemic i.p . administration of crystalline penicillin (Pc) were examined in imp-DAK rats . In all the rats used, nonconvulsive seizures characterized by bursts of spike and wave discharges (SWD) in the neocortex occurred spontaneously . A single i.p . injection of Pc at doses of 1,000,000, 1,500,000 or 2,000,000 IU/kg resulted in a transient increase in SWD activity . For the latter two doses, Pc injections also induced convulsive activity, i.e . single spikes and trains of spikes accompanied by myoclonies . When 1,500,000 IU/kg of Pc was administered repeatedly (six injections, one every 48 h), the amount of the convulsive activity induced by successive injections decreased but the increase in the number of SWD bursts became more pronounced . This result gives rise to some questions about the development of tolerance to the epileptogenic Pc effects in the course of repeated administration of this antibiotic.

Med Pregl, 1995, 48(3-4), 108 - 10
{Chronic urticaria caused by penicillin . Results of monitoring cases of acute penicillin urticaria which developed into chronic urticaria}; Poljacki M et al.; Penicillin is known to cause allergic reactions with different clinical manifestations and possible immunologic mechanisms . The purpose of this study was to follow cases of established hypersensitivity to penicillin and its possible development into chronic urticaria . 35 patients with a clinical picture of acute urticaria and with or without angioedema were examined . Three kinds of tests to penicillin were performed: patch test, scarification test and PPL test . Hypersensitivity to penicillin was confirmed in 12 (34.27%) patients with positive PPL test . Seven (58.33%) out of these 12 developed the clinical picture of chronic urticaria . As food was assumed to be the hidden source of penicillin, eliminatory diet was included . In 4 (57.14%) patients there was a complete remission of the disease during the course of diet without milk and milk products (intradermal test to milk and specific IgE antibodies were negative) . The gathered results show that acute urticaria caused by penicillin can get a chronic character . It is the consequence of prolonged penicillin's activity in some so called "hidden sources of penicillin".

Bioorg Med Chem, 1995 Jan, 3(1), 95 - 100
Synthesis and elastase inhibitory activity of 6 alpha-chloro-2,2-dimethyl-3 alpha-(pivaloyloxy)methylpenam sulfone, 6 alpha-chloro-2,2-dimethyl-3-exo-methylenepenam sulfone, benzyl and methyl 6 alpha-substituted penicillanate sulfones; Boschetti CE et al.; The triflates and pivalates of 3 alpha-hydroxymethyl-6-substituted-2,2-dimethylpenam sulfones 3, 5; methyl and benzyl 6-substituted penicillanates 6-9 and 3-exo-methylene-6-substituted-2,2-dimethylpenam sulfone 4 were synthesized . These novel compounds were evaluated as elastase inhibitors using porcine pancreatic elastase . The effects that structural modifications of substituents on C-3 and C-6 in the penam nucleus have on elastase activity were examined and several similarities and distinctions were identified when compared to the reported penicillin esters and amides elastase inhibitors.

Infection, 1995, 23 Suppl 2, S83 - 6
5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy . Cefixime Study Group; Adam D et al.; In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg cefixime/kg body weight once daily for 5 days or 20,000 I.U . penicillin V/kg body weight t.i.d . for 10 days . One hundred fifty-one children were evaluable for clinical efficacy . In the cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed . Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed . Elimination of initial pathogens occurred in 57 (82.6%) patients treated with cefixime and in 60 (88.2%) treated with penicillin V . At 3 to 4 weeks after the end of treatment, six relapses were seen in the cefixime group and eight in the penicillin V group . Mild-to-moderate adverse events that were possible related to the medication were seen in four children treated with cefixime and in five treated with penicillin V.

Dent Clin North Am, 1995 Jan, 39(1), 93 - 112
Clinical management of the avulsed tooth; Trope M; Treatment outside the dental office: Replant immediately after gentle washing if practical . If replantation is not practical, store the tooth in the best medium available . Storage media in order of preference are Hank's Balanced Salt Solution (HBSS), milk, saline, and saliva (buccal vestibule) . Water is the least desirable storage medium . Treatment in the office: Emergency visit; Place tooth in HBSS while exam is conducted and history is taken . Prepare socket for gentle repositioning of the tooth . Prepare the root . Extraoral dry time < 20 minutes: Closed apex--replant immediately after gentle washing . Open apex--soak in 1 mg doxycycline in 20 mg saline for 5 minutes . Extraoral dry time 20 to 60 minutes: Soak in HBSS for 30 minutes and replant . Extraoral dry time > 60 minutes: soak in citric acid, 2% stannous fluoride, and doxycycline and replant . Endodontics can be done extraorally . Semirigid splint for 7 to 10 days . (If alveolar fracture is present, rigid splint for 4 to 8 weeks) . Suture soft-tissue lacerations, particularly in the cervical area . Administer systemic antibiotics (penicillin V potassium if possible) Chlorhexidine rinses and stringent oral hygiene while the splint is in place (7 to 10 days) . Analgesics as required . Second visit after 7 to 10 days: Endodontic treatment: Tooth with open apex and extraoral dry time of < 60 minutes: No endodontic treatment initially . Recall every 3 to 4 weeks to examine for evidence of pathosis . If pathosis is noted, disinfect the pulp space and start apexification procedure . Tooth with open apex and extraoral dry time > 60 minutes: If endodontics was not completed in the emergency visit, start endodontics and follow apexification procedure . Tooth with closed apex: Endodontics should be initiated after 7 to 10 days . Careful chemomechanical instrumentation under strict asepsis . Splint removed at end of visit . Obturation visit: If endodontics was initiated 7 to 10 days after the avulsion, obturation can take place after short-term calcium hydroxide treatment . If endodontics was initiated more than 14 days after the avulsion or inflammatory resorption, long-term calcium hydroxide for 6 to 24 months, obturated when an intact lamina dura is traced . Restorations: Temporary restorations: Should be 4 mm deep . Reinforced zinc-oxide-eugenol, acid-etch composite resin, glass-ionomer cement . Permanent restoration: Placed immediately after obturation . Acid-etch resin and dentin bonding agents . Follow-up care: Twice per year for 3 years and yearly for as long as possible . Late complications are common.

Nervenarzt, 1995 Jan, 66(1), 54 - 6
{Organic origin of maniform psychosis . A case example of progressive paralysis}; Bschor T et al.; A 36-year-old patient with a highly developed manic-type psychosis is presented . The precise, thorough psychopathological examination indicated organic illness . The diagnosis of neurosyphilis was established when specific CNS-derived immunoglobulin was detected . The existence of increased general inflammatory parameters in the CSF indicated that the condition was active . Treatment with penicillin resulted in clear improvement of laboratory findings, but clinical recovery was only partial.

Ann Neurol, 1995 Jan, 37(1), 127 - 35
Staggering gait in medical history; Schiller F; Drunkenness and senility were recognized early as the basis of a staggering gait . To these were added venereal excesses, hence syphilis . Medical and scientific concerns began to be focused on "locomotor ataxia" in the 19th century with the systematic development of neuroanatomy and physiology . Rolando and Flourens were followed by Romberg and Todd, and later Friedreich, who all gave the spinal cord temporal precedence as a culprit over the cerebellum--and there were some forerunners . New spinal sensory pathways were delineated by Goll, Flechsig, and Gowers . In France, we must specially credit Duchenne as well as Bouillaud, and later Babinski, Marie, and Dejerine, for correcting, differentiating, extending, and underpinning current concepts . Failures of input and output, of conduction and central coordination were invoked and explained, among them the vestibular apparatus, as well as the causation by neoplasms, demyelination, degeneration, and infarction affecting even the frontal lobe, thalamus, and basal ganglia . Clinical testing was brought up to 20th-century standards essentially by Sherrington and Barany, followed by Dandy, the neurosurgeon who showed how to replace ventricular fluid by air, more recently made obsolete by modern roentgenographic procedures . And tabes dorsalis, once the chief culprit, has practically become a medical anachronism thanks to penicillin.

Arch Otolaryngol Head Neck Surg, 1995 Jan, 121(1), 39 - 43
Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla; Jakob T et al.; BACKGROUND: Currently available topical otic preparations contain a variety of antibiotics and other ingredients that are potentially damaging to the middle and inner ear . There is therefore a need to identify agents that are safe as well as effective for topical otologic use . In pursuit of that goal, we used an animal model to evaluate the ototoxic potential of the broad-spectrum, penicillin derivative ticarcillin--both alone and combined with clavulanic acid (a beta-lactamase inhibitor) . METHODS: Twenty chinchillas served as subjects . Ten of the animals were given a single middle ear application of ticarcillin; the remaining 10 animals received ticarcillin disodium plus clavulanate potassium (Timentin) . Five animals from each of the two groups were killed after 1 week to assess short-term effects and the other five animals in each group were kept for 4 weeks before their temporal bones were removed for histologic study . RESULTS: Significant toxic effects, involving both the middle and inner ear, were observed in all experimental groups . Alterations of the middle ear at 1 week included inflammation, hemorrhage, and effusions . Middle ear cholesteatomas were observed at 4 weeks . Inner ear changes seen at 1 and 4 weeks included hair cell loss, supporting cell degeneration, and strial damage . CONCLUSION: The study results indicate that ticarcillin should not be considered for further evaluation as a possible antibiotic for use in ototopical preparations.

Avian Dis, 1995 Jan-Mar, 39(1), 191 - 3
Erysipelas in quail and suspected erysipeloid in processing plant employees; Mutalib A et al.; Erysipelas was diagnosed in two commercial breeder flocks of Coturnix quail and was characterized clinically by sudden mortality . At necropsy, lesions comprised generalized congestion, hemorrhages in the thigh and breast muscles, swelling of liver, spleen, and kidney, and dark red edematous lungs . Erysipelothrix rhusiopathiae was cultured from visceral organs of affected birds . Medication with penicillin in the drinking water controlled the mortality . A possible source of infection was fish raised on the premises . Seven people at the quail processing plant developed localized inflammation of the fingers, which responded when antibiotic therapy for erysipeloid was initiated.

Eksp Klin Farmakol, 1995 Jan-Feb, 58(1), 54 - 7
{The effect of D-penicillamine on the metabolism of the basic substance of the connective tissue and the indices of the liver parenchyma in experimental cirrhosis in rats}; Skobeleva TV; While examining the effects of D-penicillamine {correction of D-penicillin} on the formation of hepatic toxic damage in mature male Wistar rats from the stage of developing cirrhosis to that of the developed one, the author revealed a high antifibrotic activity of the drug which significantly normalized the metabolism of the major agent of the hepatic connective tissue; there was a slight improvement of parenchymal metabolism when the agent was taken for 2 months . There were apparently healthy animals in the experimental group following 4-month course of the therapy . Control rats developed hepatic damage, as evidenced by electron microscopic studies.

Scand J Infect Dis, 1995, 27(1), 29 - 31
Treatment of louse-borne relapsing fever with low dose penicillin or tetracycline: a clinical trial; Seboxa T et al.; A clinical trial was conducted in order to evaluate the efficacy of procaine penicillin and tetracycline, respectively, in the treatment of louse-borne relapsing fever . 184 patients (160 men, 24 women) admitted to the Gondar hospital during the rainy season 1992 were assigned to 1 of 4 treatment groups: procaine penicillin 100,000 (PP100), 200,000 (PP200) or 400,000 (PP400) international units (IU) intramuscularly (i.m.), or tetracycline 250 mg per os (TTC, p.o.) . All drugs were given as single doses . The overall case fatality rate was 3.3% . Frequency of relapses, Jarisch-Herxheimer-like reactions (JHR) and deaths were significantly different between patients treated with TTC and those treated with PP100 . Relapses occurred most often in the group receiving the lowest dose of penicillin (46%), and decreased with increasing dosage of penicillin; none of the patients treated with TTC had a relapse . Occurrence of JHR showed the opposite pattern: whilst 2 (5%) patients treated with PP100 developed a JHR, 16 (29%) in the PP200 group, 10 (31%) in the PP400 group, and 27 (47%) in the TTC group developed a JHR . As mortality is linked to severe JHR, and most relapses are clinically mild and easily treated, these results speak in favour of using low-dose penicillin to initiate the treatment of relapsing fever.

Biotechnol Prog, 1995 Jan-Feb, 11(1), 93 - 8
Pellet formation and fragmentation in submerged cultures of Penicillium chrysogenum and its relation to penicillin production; Nielsen J et al.; The spores of Penicillium chrysogenum are of the noncoagulating type, and after spore germination a culture of disperse mycelia is obtained . In this study, it is shown that when the hyphal elements increase in size, they may agglomerate, and depending on the operating conditions, these agglomerates may develop into pellets with a dense core . The influence of initial spore concentration and agitation rate on agglomeration, leading to pellet formation, was studied . For a low concentration of spores in the inoculum, only a few hyphal elements agglomerate and pellets with a small diameter are obtained . At higher spore concentrations, many hyphal elements agglomerate and develop into large diameter pellets . Finally, at a very high spore concentration in the inoculum, the final hyphal element size is small and agglomerates therefore are not formed . With a high agitation rate, the agglomeration of hyphal elements is reduced . In a repeated fed-batch cultivation, where there was a shift from pellet morphology to disperse mycelia, it was found that there is no relation between macroscopic morphology and penicillin production by P . chrysogenum . The morphology was quantified throughout the repeated fed-batch cultivation, and both the pellet diameter and the concentration of pellets were affected by the agitation rate.

Turk J Pediatr, 1995 Jan-Mar, 37(1), 67 - 71
Gangrene after penicillin injection (a case report); Ozel A et al.; A patient with right lower limb gangrene that developed after penicillin injection is presented . Accidental intraarterial administration of penicillin may cause gangrene necessitating amputation . To avoid this severe complication, every intramuscular injection should be given with meticulous attention to proper technique, with adequate restraint of the patient, and with full knowledge of local anatomy and potential complications.

Vasa, 1995, 24(1), 72 - 6
{Aneurysm of the descending thoracic aorta in tertiary syphilis}; Mickley V et al.; A 53-year-old female presented with septicaemia caused by left ureteric obstruction due to ureterolithiasis . Further diagnostic work-up for left mediastinal widening revealed an asymptomatic aneurysm of the descending aorta . Serologic tests for syphilis were highly positive (TPHA 1:10240, 19s-IgM-FTA-Abs 1:20, Cardiolipin KBR 1:72 IU/ml) . After a three weeks course of Penicillin G, 19s-IgM-FTA-Abs was negative . A successful tube resection of the aneurysm was performed . The diagnosis of luetic aneurysm of the descending aorta was confirmed histologically . Although rare today, tertiary syphilis should be considered in the differential diagnosis of thoracic aneurysm in middle-aged patients lacking classical risk factors for atherosclerosis . The immune pathogenesis of cardiovascular syphilis still remains subject of controversy.

Sex Transm Dis, 1995 Jan-Feb, 22(1), 31 - 8
Treponemicidal antibody measured by the "washed-killing" assay correlates with immunity in experimental rabbit syphilis; Lewinski MA et al.; BACKGROUND AND OBJECTIVES: The authors have previously shown that complement-dependent treponemicidal antibody measured by the "washed-killing" assay is directed exclusively against surface-exposed targets on Treponema pallidum, presumably the Treponema pallidum rare outer membrane proteins detected by freeze-fracture electron microscopy . GOAL OF THIS STUDY: Because immune mechanisms against Treponema pallidum rare outer membrane proteins are likely to be central to a protective host response, it was examined whether a relationship could be established between treponemicidal levels as measured by the "washed-killing" assay and host immunity in experimental syphilis . STUDY DESIGN: Three groups of Treponema pallidum-infected rabbits were treated curatively with penicillin at 9 days, 30 days, and 6 months post-infection to generate animals with varying degrees of immunity to challenge re-infection . The level of complement-dependent treponemicidal activity in sera obtained before infection (basal) and before intradermal challenge was determined by the "washed-killing" assay and compared with that detected using conventional in vitro immobilization . RESULTS: Using the "washed-killing" assay, a close quantitative correlation as measured by a treponemal immobilizing endpoint titer was demonstrable between prechallenge treponemicidal antibody and the status of immunity to re-infection . Sera from rabbits completely susceptible to symptomatic and disseminated asymptomatic re-infection lacked treponemicidal antibody . Sera from challenged rabbits with a relatively low degree of immunity to symptomatic disease showed endpoints of < or = 4 . Rabbits with a relatively high degree of immunity to symptomatic reinfection and resistant to disseminated disease had endpoints that ranged from 6 to 96 . Rabbits completely resistant to challenge exhibited endpoints ranging from 96 to 128 . CONCLUSION: Treponemicidal antibody measured by the "washed-killing" assay correlated closely with the status of immunity in experimental rabbit syphilis . Thus, antibody measured by this assay may be directed against key protective Treponema pallidum surface immunogens.

Wien Med Wochenschr, 1995, 145(7-8), 191 - 4
{Neurosyphilis . A case report and review of the literature on differential neuroborreliosis diagnosis}; Zifko U et al.; A 35-year old man was presented with organic psychosyndrome . Anamnestic reports informed about changes in his behaviour like loss of interest, reduced concentration and short-term-memory loss within the last 2 years . The practicing psychiatrist diagnosed a depressive syndrome in conjunction with a borderline syndrome and administered antidepressive and neuroleptic therapy . Specific serologic tests were not done . Neurologically, there was a picture of influent and slurred speech, and ataxic gait . Muscle tonus was normal, muscle reflexes were of the same diminished intensity on both sides . The psychic status revealed a person mostly oriented in time, location and situation but with severe disorders of recognition, concentration, and memory . Laboratory diagnosis proved the suspected diagnosis of neurosyphilis . Additionally, there were antibodies to Borrelia burgdorferi (Bb) in serum and CSF and a positive CSF/serum index of 9.0 (threshold: 1.9) . The neuroradiologic examination (CCT, NMR, SPECT) showed an intense, diffuse, frontotemporal atrophy of the cortex . By NMR, massive gliosis was found in both hippocampi . Angiographically, an aneurysma (1 cm in diameter) of the medial cerebral artery was demonstrated . Specific treatment was performed with Na penicillin (5 Mio . i.v./4 h over 21 days) . No remission could be achieved.

Patol Fiziol Eksp Ter, 1995 Jan-Mar, (1), 12 - 4
{Effect of hyperactivation of the somatosensory cortex on pain syndrome of spinal origin in rats}; Igon'kina SI et al.; The cortical effects were studied in rats with abnormal pain . The spinal pain syndrome was induced by a generator of abnormally enhanced excitation in spinal dorsal cord . Hyperactivation of the somatosensory cortex was caused with penicillin . Cortical hyperactivation was shown to lead to the suppression of the pain syndrome.

Life Sci, 1995, 57(1), PL7 - 12
Time-related antiepileptic effects of the synthetic glucocorticoid dexamethasone in rat hippocampal slices; Sagratella S et al.; The in vitro antiepileptic activity of the synthetic glucocorticoid dexamethasone (DEX) was tested in rat hippocampal slices on the CA1 epileptiform activity induced by sodium penicillin (PEN) . Slice perfusion with 1 mM PEN produced within 60 min the development of a CA1 epileptiform bursting made up of an increase of the primary CA1 population spike followed by the appearance of secondary epileptiform population spikes . Slice perfusion with 100 microM DEX together with PEN (1 mM) partially prevented but did not block the expression of the CA1 epileptiform bursting as evidenced by a significant (P < 0.05) reduction of the duration of the bursting due to the epileptogenic agent . Slice perfusion with 50 microM DEX together with PEN (1 mM) failed to prevent or block the expression of the CA1 penicillin-induced epileptiform bursting . A 60 min slice pretreatment with 50-100 microM DEX followed by a slice perfusion with 50-100 microM DEX together with PEN (1 mM) prevented the expression of the CA1 epileptiform bursting . Cycloheximide (1 microM), a protein synthesis inhibitor, perfused together with DEX reverted the inhibitory effects of dexamethasone on the expression of the penicillin-induced CA1 epileptiform bursting . The results indicate that the synthetic glucocorticoid DEX presents concentration- and time-related in vitro antiepileptic effects . In addition, the data suggest that this inhibitory effect occurs via a protein synthesis-dependent mechanism.

Rev Laryngol Otol Rhinol (Bord), 1995, 116(3), 195 - 7
{Cervico-facial cellulitis of oral and dental origin: study of 26 cases at the Lomé University Hospital}; Kpemissi E; The authors report 26 cases of cervico-facial cellulitis of mouth and dental origin . They highlight the severity of those affections . The original entry is dental caries in 88.4% of cases . Adequate treatment consisting of a surgical drainage, a suppression of the original entry and antibiotherapy combining a penicillin, an aminoglycosid and metronidazol . Preventive therapeutic measures are prescribed.

Connect Tissue Res, 1995, 33(1-3), 97 - 103
Temperature sensitive simian virus 40 large T antigen immortalization of murine odontoblast cell cultures: establishment of clonal odontoblast cell line; MacDougall M et al.; During tooth formation instructive epithelial-mesenchymal interactions result in the cytodifferentiation of ectomesenchymal cells into odontoblasts which produce the dentin extracellular matrix (DECM) . The purpose of our study was to establish a stable murine odontoblast cell line by immortalization of odontoblasts using retrovirus transfection . In order to accomplish this goal, we utilized a previously characterized odontoblast monolayer cell culture system supportive of odontoblast cytodifferentiation from dental papilla mesenchyme (DPM), expression and secretion of a DECM and dentin biomineralization . First mandibular molars from E-18 Swiss Webster mice were dissected, the DPM isolated, and pulp cells dissociated . Pulp cells (5 x 10(5)/well) were plated as monolayers and grown in alpha-MEM supplemented with 10% FCS, 100 units/ml penicillin and streptomycin, 50 micrograms/ml ascorbic acid . Cultures were maintained for 6 days at 37 degrees C in a humidified atmosphere of 95% air and 5% CO2, with media changes every two days . Immortalization was performed using a recombinant defective retrovirus containing the temperature sensitive SV-40 large T antigen cDNA and the neomycin (G418) resistance gene recovered from CRE packaging cells . Cultures were infected for 24 h with CRE conditioned medium containing 8 micrograms/ml of polybrene, the media was replaced with selective media containing 300 micrograms/ml of G418, and the cultures incubated at 33 degrees C for one month with media changes every 3-5 days . Neomycin resistant cells were cloned by serial dilution to single cells in 96-well culture plates and grown in selection medium at 33 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalogr Clin Neurophysiol, 1995 Jan, 94(1), 80 - 5
Refractory periods following interictal spikes in acute experimentally induced epileptic foci; Dorn T et al.; Under epileptic conditions, interictal epileptic events are followed by large inhibitions which prevent the transition to ictal discharges . In the present experiments the refractory period following interictal epileptic spikes was investigated in animal experiments . Interictal epileptic activity was elicited by application of penicillin onto the motor cortex of anesthetized rats . Interictal epileptic discharges were followed by an absolute refractory phase lasting 200-300 msec, in which no epileptic event could be elicited by epicortical stimulation . This was followed by a relative refractory period up to 900 msec after onset of the conditioning spike; spikes elicited with intervals between 300 and 900 msec were smaller than those with greater intervals and required higher stimulation intensities . This period ends by a sharp drop of threshold . In two-thirds of the experiments, spikes were favoured in intervals of 300-500 msec due to a sag of the threshold, which possibly indicates recurrent neuronal excitations . Stimulations with frequencies of about 1/sec favoured a transition from a pattern with spikes appearing in an irregular sequence every 2-3 sec, to a discharge pattern with spikes appearing with regular intervals of about 1 sec . This change of firing pattern was associated with a drop of the spike threshold . It is concluded that interictal epileptic events are followed by a refractory period comprising different components . Alterations of the neuronal inhibitions responsible for these refractory phases may be critical for the activity of the focus and may determine the transition from interictal to ictal discharges.

Eur J Pharmacol, 1994 Dec 27, 271(2-3), 259 - 63
Felbamate displays in vitro antiepileptic effects as a broad spectrum excitatory amino acid receptor antagonist; Domenici MR et al.; The in vitro antiepileptic activity of the novel anticonvulsant drug felbamate was tested in rat hippocampal slices on the CA1 epileptiform bursting induced by different chemical epileptogenic agents . The effects of felbamate were compared with those of the anticonvulsant drugs diphenylhydantoin and pentobarbitone and with the effects of excitatory amino acid antagonists acting at both N-methyl-D-aspartate (NMDA) and non-NMDA receptors . Like the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), felbamate at a minimum effective concentration of 1 mM induced a significant (P < 0.01) reduction of the duration of the CA1 epileptiform bursting due to the K+ channel blocker, 4-aminopyridine, and the excitatory amino acids, kainate and quisqualate . Like the NMDA receptor antagonist ketamine, felbamate (1.6 mM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions . Conversely, felbamate (1.6 mM), CNQX (100 microM) and ketamine (100 microM) failed to affect the epileptiform bursting induced by the GABA antagonist penicillin . Pentobarbitone (100 microM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions, 4-aminopyridine or penicillin, while diphenylhydantoin (up to concentrations of 100 microM) failed to have an effect . The results indicate that felbamate displays a unique profile of in vitro antiepileptic effects as a broad spectrum antagonist of excitatory amino acid transmission.

Neuroreport, 1994 Dec 20, 5(18), 2454 - 6
Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide; Marangoz C et al.; The effect of sodium nitroprusside (SNP) on epileptiform activity elicited by administration of penicillin (500 units) into the somatomotor cortex was studied in anaesthetized rats . No epileptiform activity was observed after intracortical microinjection of SNP (5 and 20 nM) . Microinjection of penicillin into the somatomotor cortex induced epileptiform activity in electrocorticograms (ECoG) . Epileptiform discharges elicited by penicillin were significantly decreased by SNP . The effect of SNP appeared within 1 min of application and lasted for 2-5 min . The inhibitory effect of SNP on epileptiform activity could be prevented by pretreatment with methylene blue (20 nM), a soluble guanylate cyclase inhibitor . Prior injection of haemoglobin (5 microliter), a nitric oxide (NO) scavenger, prevented the anticonvulsant effect of SNP . These results suggest that NO may be an endogenous anticonvulsant substance.

Neurosci Lett, 1994 Dec 5, 182(2), 259 - 62
Amphetamine and haloperidol modulatory effects on Purkinje cell activity and on EEG power spectra in the acute rat model of epilepsy; Culic M et al.; The modulation of cerebellar Purkinje cell activity and EEG from parietal cortex was studied in the rat model of epilepsy induced by penicillin under acute haloperidol and amphetamine treatment . The discharge pattern of Purkinje cells showed tendency towards inhibition and EEG power spectra increased after parenteral administration of penicillin (1000000 IU/kg, i.p.) . Acute haloperidol treatment (1 mg/kg, i.p.), performed after the development of penicillin induced epileptic episodes, elicited a prominent excitation of Purkinje cell discharges associated with parallel increase in mean EEG power spectra . However, acute DL-amphetamine treatment induced marked suppression of Purkinje cell discharges as well as outstanding decrease of the mean EEG power spectra . These results indicate that cerebellar Purkinje cells may be important in the control of seizure activity and that noradrenergic influences are relevant.

Scott Med J, 1994 Dec, 39(6), 175 - 7
Gonorrhoea in Aberdeen: a serovar analysis; Ross JD et al.; The serotyping of gonococcal isolates has enabled detailed studies of the epidemiology of gonorrhoea in different geographical areas . This study reports the patterns of infection found in 1992 in Aberdeen and relates these to a variety of clinical parameters . 140 cases of gonorrhoea were isolated the majority of which belonged to one strain (lA-2) in contrast to the diversity of strains seen in other Scottish cities . Most isolates were highly sensitive to penicillin and only 3 penicillinase producing strains were found . A low rate of infections in homosexual men is reported again in contrast to the situation seen in other geographically close cities . Compared to the rest of Scotland Aberdeen has a high prevalence of gonorrhoea.

Am J Physiol, 1994 Dec, 267(6 Pt 3), S113 - 9
Certainty and uncertainty in science: the subjectivistic concept of probability in physiology and medicine; Jevning R et al.; Most physiological scientists have restricted understanding of probability as relative frequency in a large collection (for example, of atoms) . Most appropriate for the relatively circumscribed problems of the physical sciences, this understanding of probability as a physical property has conveyed the widespread impression that the "proper" statistical "method" can eliminate uncertainty by determining the "correct" frequency or frequency distribution . However, many relatively recent developments in the theory of probability and decision making deny such exalted statistical ability . Proponents of Bayes's subjectivist theory, for example, assert that probability is "degree of belief," a more tentative idea than relative frequency or physical probability, even though degree of belief assessment may utilize frequency information . In the subjectivist view, probability and statistics are means of expressing a consistent opinion (a probability) to handle uncertainty but never means to eliminate it . In the physiological sciences the contrast between the two views is critical, because problems dealt with are generally more complex than those of physics, requiring judgments and decisions . We illustrate this in testing the efficacy of penicillin by showing how the physical probability method of "hypothesis testing" may contribute to the erroneous idea that science consists of "verified truths" or "conclusive evidence" and how this impression is avoided in subjectivist probability analysis.

Am J Gastroenterol, 1994 Dec, 89(12), 2227 - 9
Gastric syphilis: a disease with multiple manifestations; Atten MJ et al.; The resurgence of syphilis in the United States is effecting all areas of medical care . We describe a young female presenting with symptoms of peptic ulcer disease who failed to respond to H2-receptor antagonist therapy . After further evaluation, she was diagnosed with gastric syphilis and responded well to penicillin . Because gastric syphilis has no pathognomonic clinical findings, the clinician needs to be aware of this disease entity so as to make the correct diagnosis and institute the appropriate antibiotic therapy.

N Engl J Med, 1994 Dec 1, 331(22), 1469 - 73
The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection; Gordon SM et al.; BACKGROUND . Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment . We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis . METHODS . Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid . We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine . Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days . Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum . RESULTS . In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results . In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations . One patient relapsed with meningovascular syphilis six months after therapy . T . pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens . CONCLUSIONS . In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop . The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Analyst, 1994 Dec, 119(12), 2727 - 9
Improved spectrophotometric assay for beta-lactam residues in kidney tissue; Everest DJ et al.; This paper describes a detection system for beta-lactams using a commercially prepared carboxypeptidase enzyme (CPase) and a substrate system in which lactic acid is cleaved from a synthetic peptide, N alpha-N epsilon-diacetyl-L-lysyl-d-alanyl-d-lactic acid . The lactate is itself oxidized by lactate dehydrogenase to form NADH . Oxidized NAD+ is regenerated by diaphorase with the simultaneous reduction of the colourless 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride hydrate (INT) indicator substrate to produce a red-mauve colour that is proportional to CPase activity . The presence of beta-lactams decreases the intensity of colour produced . The lower limit of detection for benzyl penicillin (Pen G) by this system is 20 ng g-1 compared with 50 ng g-1 by the same assay but using a R-d-ala-d-ala substrate from a commercial kit.

Analyst, 1994 Dec, 119(12), 2595 - 601
Confirmatory assay for the simultaneous detection of five penicillins in muscle, kidney and milk using liquid chromatography-electrospray mass spectrometry; Blanchflower WJ et al.; A confirmatory assay using liquid chromatography-electrospray mass spectrometry (LC-EMS) is presented for the simultaneous determination of penicillins V and G along with oxacillin, cloxacillin and dicloxacillin in muscle, kidney and milk . Nafcillin is used as an internal standard . Samples are extracted using acetonitrile and cleaned up using liquid-liquid extraction into dichloromethane . The extracts are injected into a dedicated LC-EMS instrument and any penicillins present are detected using multiple single-ion monitoring . Three or four ions can be detected for each penicillin, meeting one of the recommended EU criteria for confirmatory residue analyses using low-resolution mass spectrometry . The detection limits are below the stipulated EU maximum residue limits for each of the penicillins.

Hautarzt, 1994 Dec, 45(12), 834 - 44
{Contact allergies in medical occupations}; Rustemeyer T et al.; Based on reports in the literature, data from the information network of German dermatology centres (Informationsverbund Dermatologischer Kliniken) and the authors own findings, a review is presented on prevalence, clinical picture and causative agents of contact allergic dermatoses in health care professions . In 1991 the proportion of suspected occupational diseases in the health care professions (including hairdressers) represented by cases of dermatitis, as reported to the responsible insurance institution, reached 72% of the total for the year (7287 out of 10127) . Every 20th to 40th case was recognized as an occupational dermatosis according to German law . Accurate figures on incidence are scarce; for dentists an incidence of 0.11% has been calculated . The risk of developing occupational hand eczema has been shown to be at least three times higher for nurses than for other so-called dry professions . For persons engaged in the personal care of the ill and the elderly, relevant occupational allergens were found to be benzalkonium chloride and aldehydes in disinfectants, as well as rubber accelerators such as thiuram mix . Latex contact urticaria has increasing significance for medical personnel, with prevalence rates of sensitization between 4.5% and 10.7% . Among physicians, contact allergies to thiuram mix were found to be dominant (12.9%) . For surgeons and orthopaedic surgeons, methyl methacrylate as a constituent of bone cement is of great importance . Various esters of acrylic acid and methacrylic acid are important sensitizers in the dental professions, particularly in heavily exposed dental laboratory technicians . Only a few gloves protect against these types of sensitizers . Sensitizations by medicaments can be avoided in most cases by reducing direct skin contact, as practiced with penicillin or ispaghula powder . Strategies of prevention include information of atopics regarding the increase in occupational dermatitis, the regular use of barrier creams, intensive skin care after work and avoidance of irritants and allergens wherever possible.

Biotechnol Appl Biochem, 1994 Dec, 20 ( Pt 3), 357 - 69
Industrial design of enzymic processes catalysed by very active immobilized derivatives: utilization of diffusional limitations (gradients of pH) as a profitable tool in enzyme engineering; Guisan JM et al.; We have developed integrated studies of enzyme reaction engineering for the hydrolysis of penicillin G catalysed by very active penicillin G acylase (PGA) derivatives . We have studied the distinct effect of a key variable (pH) on different industrial parameters (e.g . activity/stability parameters) . In this way we have demonstrated, in contrast with that proposed by other authors, that the generation of gradients of pH inside the porous structure of very active enzyme derivatives may be not a problem but a 'very profitable tool' to improve the whole set of industrial parameters . In this way we can establish two distinct 'optimal pH values': (i) the one inside the particle of the biocatalyst and (ii) the one in the bulk solution . The use of an external pH of 8.0 associated with the promotion of a controlled decrease in internal pH (e.g . around a mean value of 5.5) was very useful to simultaneously obtain interesting values of all industrial parameters: (i) very high hydrolytic yields (higher than 97%); (ii) a very important increase on the stability of PGA derivatives (higher than a 50-fold factor); and (iii) a very small decrease in operational activity (approximately 15%) as compared with the one of soluble enzyme at pH 8.0 with no diffusional hindrances.

Biotechnol Appl Biochem, 1994 Dec, 20 ( Pt 3), 313 - 22
Immobilized-metal-chelate regenerable carriers: (I) . Adsorption and stability of penicillin G amidohydrolase from Escherichia coli; Anspach FB et al.; Penicillin G amidohydrolase (PGA) was immobilized on Cu(II)-chelate regenerable sorbents . A long spacer was essential for binding, such as bisoxirane in the case of Sepharose 4B or glycidoxypropyltrimethoxysilane in the case of silica-based carriers . The stability of the PGA-carrier was determined both by the interaction forces between PGA and the metal-chelate sorbent and the presence of penicillin G (Pen G) . The force of interaction between the enzyme and the metal-chelate sorbent was low, and Pen G competed for binding sites at high concentrations . The carrier with a small pore size demonstrated diffusion restrictions during immobilization of PGA, resulting in low activities of the immobilized enzyme . This carrier could not be completely regenerated . Carriers with an average pore size of 55 nm or larger displayed fewer diffusion restrictions . The corresponding Cu(II)-chelate sorbents were regenerated several times.

Appl Environ Microbiol, 1994 Dec, 60(12), 4432 - 9
A reporter gene analysis of penicillin biosynthesis gene expression in Penicillium chrysogenum and its regulation by nitrogen and glucose catabolite repression; Feng B et al.; Vectors which possess a truncated niaD gene encoding nitrate reductase were developed to allow targeted gene integration during transformation of an niaD mutant Penicillium chrysogenum host . The Penicillium genes pcbC and penAB are immediately adjacent to each other and are divergently transcribed, with an intergenic control region serving as their promoters . Gene fusions were constructed with a reporter gene, uidA, which encodes beta-glucuronidase . The pcbC-penAB intergenic region was fused to the uidA gene in both orientations so that regulated expression of each structural gene could be investigated . These fusion genes were targeted to the chromosomal site of the niaD locus of P . chrysogenum, and their expression was examined under different growth conditions . The expression of each of these penicillin biosynthesis genes was found to be regulated by nitrogen repression, glucose repression, and growth stage control.

Hua Xi Yi Ke Da Xue Xue Bao, 1994 Dec, 25(4), 452 - 5
{Studies of enzyme-linked immunoassay for testosterone using penicillinase as label}; He J et al.; An enzyme-linked immunoassay (EIA) for testosterone was developed based on penicillinase as the marker enzyme . The assay proposed requires a conjugate containing penicillinase as the enzymatic component, penicillin Vas substrate and an iodine-starch reagent as the chromogenic component . The binding of conjugate molecules results in the transition of the iodic complex from dark blue to colourless . delta A (the difference between the blank and the testosterone) vs log C was linear over the range 10(-7) - 10(-2)mg/ml (r = 0.9969), with a limit of detection 25 pg per disc . The CVs of day to day and within day for plasma testosterone were < 3.3% and 5.9%, respectively . There was a good correlation between the values obtained by EIA and radioimmunoassay (r = 0.937).

Acta Paediatr, 1994 Dec, 83(12), 1276 - 81
Helicobacter pylori infection in children with recurrent abdominal pain; Wewer V et al.; Helicobacter pylori was cultured and Helicobacter-like organisms (HLO) were seen in 6 (16%) of 37 children with recurrent abdominal pain . Five children had concomitant histological inflammation, but none had endoscopic changes . All 6 children demonstrated positive serology . Compared with the total group, they were more often from developing countries, larger families and lower social groups . Treatment with phenoxymethyl penicillin and colloidal bismuth subcitrate did not result in side effects or elevated serum levels of serum bismuth . Three children demonstrated metronidazole-resistant strains and the treatment of these children remained an unsolved problem . Among the 31 H . pylori/HLO negative children 8 (26%) demonstrated histological changes, 5 (16%) endoscopic changes and 11 (35%) had positive serology . In conclusion, pathological findings at upper gastrointestinal endoscopy are common in children with recurrent abdominal pain . Because of disconcordance between endoscopy, histology and culture, we recommend that biopsies should always be taken to clarify the diagnosis.

Arch Dis Child, 1994 Dec, 71(6), 529 - 31
A survey of recommendations given to patients going home after bone marrow transplant; Brandt L et al.; A postal questionnaire was sent to 11 UK Children's Cancer Study Group bone marrow transplant centres asking them for details of their instructions to patients on discharge after either allogeneic or auto transplant; nine centres responded . There was no recommendation on which they all agreed . Though all centres gave prophylactic septrin, the times of starting and stopping treatment varied considerably . Three centres recommended lifelong penicillin after total body irradiation, one treated for two years and five gave no such prophylaxis . Four of nine centres gave routine acyclovir for herpes simplex prophylaxis . Most centres suggested prophylaxis against varicella after contact exposure for one year . However, three gave zoster immune globulin alone, one gave this together with acyclovir, and five gave acyclovir alone . No two centres recommended the same dose of acyclovir . Vaccinations were allowed from 6-18 months after transplant . One centre required documentation of recovery of immune function first . Four centres recommended a child stay off school for six months; others had 'common sense' approaches . Only one centre did not allow family holidays for the first six months but many imposed restrictions on these holidays . Dietary restrictions varied greatly between centres . It is concluded that there is a need for unified and scientifically justified guidelines after transplant for paediatric bone marrow transplant patients.

Epilepsy Res, 1994 Dec, 19(3), 215 - 20
Locus coeruleus noradrenaline system and focal penicillin hippocampal epilepsy: neurophysiological study; Ferraro G et al.; Previous experimental investigations have shown that several neuronal systems modulate the spontaneous and paroxysmal electric activity of the hippocampus . The locus coeruleus-noradrenaline (LC-NA) system exerts an inhibitory influence on several brain areas including the ipsilateral hippocampus . Selective destruction of the LC increases the susceptibility to epileptiform phenomena in different models of experimental epilepsy . Our experiments were conducted on 34 rats in which a steady epileptiform interictal activity of the hippocampus was obtained by means of intrahippocampal administration of penicillin . Electrical stimulation of LC caused a significant decrease of penicillin spiking of hippocampus . Stimulation sessions given 10-15 min after i.p . propranolol administration (2 mg/kg) failed to induce any significant modification in the hippocampal spiking frequency . Intrahippocampal injection of L-noradrenaline mimicked the inhibitory effect of LC electrical stimulation on hippocampus . Finally, intrahippocampal administration of isoproterenol HCl, a beta-adrenoceptor agonist, caused a significant decrease of hippocampal penicillin spiking; this effect was antagonised by i.p . propranolol administration . The experimental data show a modulating influence of the LC-NA system on penicillin focal hippocampal epilepsy that probably involves beta-adrenoceptors.

Antimicrob Agents Chemother, 1994 Dec, 38(12), 2905 - 7
Susceptibilities of 200 penicillin-susceptible and -resistant pneumococci to piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftazidime, and ceftriaxone; Pankuch GA et al.; MICs of eight beta-lactams (piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftazidime, and ceftriaxone) were determined by agar dilution against 64 penicillin-susceptible, 70 intermediately penicillin-resistant, and 66 fully penicillin-resistant pneumococci . The MICs of piperacillin with and without tazobactam for 90% of the susceptible, intermediately resistant, and resistant strains tested (MIC90s) were < or = 0.064, 2.0, and 4.0 micrograms/ml, respectively . By comparison, those of ampicillin with and without sulbactam were 0.125, 2.0, and 4.0 micrograms/ml and those of ceftriaxone were < or = 0.064, 1.0, and 2.0 micrograms/ml, respectively . Strains were less susceptible to ticarcillin with and without clavulanate (MIC90s, 2.0, 64.0, and 128.0 micrograms/ml) and ceftazidime (MIC90s, 1.0, 8.0, and 32.0 micrograms/ml).

Rev Med Chil, 1994 Dec, 122(12), 1393 - 7
{Neurosyphilis and human immunodeficiency virus (HIV-1)infection . Experience with 6 cases}; Silva C et al.; HIV infected population has a higher incidence of syphilis, being this an independent risk factor for HIV infection . We report 88 HIV infected patients seen during the last three years . Fourteen (16%) had reactive serum VDRL and FTA-ABS and neurosyphilis was diagnosed in six (6.8%) . Three had a treponemal uveitis-retinitis, one a meningovascular syphilis and one a secondary syphilis with meningeal and otological involvement . Patients were treated with penicillin 20 million UI/day for 14 days with good clinical and laboratory response and CSF normalization in those subjected to a second lumbar puncture . It is concluded that neurosyphilis must be considered in the differential diagnosis of neurological complications of HIV infections.

Rev Med Chil, 1994 Dec, 122(12), 1367 - 71
{Isolation of several species of the genus Aspergillus from soil of intrahospital ornamental plants}; Thompson L et al.; The earth of ornamental plants is one of the main reservoirs of Aspergillus type of fungi in hospital areas . We studied 174 ornamental interior plants from a hospital at Santiago . Samples were obtained from the soil surface and sowed in Sabouraud-glucose agar, adding streptomycin and G-penicillin . After 72 h of culture, at least one strain of Aspergillus was isolated from 140 samples (80.5%) . The most frequently isolated strain was A fumigatus (129 samples), followed by A niger (75 samples) . A fumigatus and A niger were the only isolated strains in 65 and 11 samples respectively . These findings confirm that ornamental plants can be important reservoirs of Aspergillus strains, a potential infectious agent for immunocompromised patients, in hospital areas.

Proc Natl Acad Sci U S A, 1994 Nov 22, 91(24), 11611 - 5
The 47-kDa major lipoprotein immunogen of Treponema pallidum is a penicillin-binding protein with carboxypeptidase activity; Weigel LM et al.; The recent model of Treponema pallidum molecular architecture proposes that the vast majority of the bacterium's integral membrane proteins are lipoprotein immunogens anchored in the cytoplasmic membrane while the outer membrane contains only a limited number of surface-exposed transmembrane proteins . This unique model explains, in part, the organism's remarkable ability to evade host immune defenses and establish persistent infection . Our strategy for refining this model involves demonstrating that the physiological functions of treponemal membrane proteins are consistent with their proposed cellular locations . In this study, we used an ampicillin-digoxigenin conjugate to demonstrate by chemiluminescence that the 47-kDa lipoprotein immunogen of T . pallidum (Tpp47) is a penicillin-binding protein . Reexamination of the Tpp47 primary sequence revealed the three amino acid motifs characteristic of penicillin-binding proteins . A recombinant, nonlipidated, soluble form of Tpp47 was used to demonstrate that Tpp47 is a zinc-dependent carboxypeptidase . Escherichia coli expressing Tpp47 was characterized by cell wall abnormalities consistent with altered peptidoglycan biosynthesis . Though the inability to cultivate T . pallidum in vitro and the lack of genetic exchange systems continue to impede treponemal research, this study advances strategies for utilizing E . coli molecular genetics as a means of elucidating the complex relationships between syphilis pathogenesis and T . pallidum membrane biology.

Biochem J, 1994 Nov 1, 303 ( Pt 3), 869 - 75
Changing the substrate specificity of penicillin G acylase from Kluyvera citrophila through selective pressure; Roa A et al.; Escherichia coli (muT, mutD, Leu-) cells transformed with plasmid pYKD59 harbouring the pac gene encoding penicillin acylase (PA) from Kluyvera citrophila ATCC 21285 were exposed to environmental conditions that made expression of this enzyme essential for growth . Under these conditions, spontaneous mutants were isolated that used adipyl-L-leucine as the sole source of L-leucine . DNA sequencing of the mutant pac genes identified a transversion mutation of thymine to guanine at position 1163 . This mutation was located in the beta-subunit of the enzyme and resulted in conversion of Phe-360 to valine . The assignment of this mutation to the shift in substrate specificity was further confirmed by site-directed mutagenesis . Secondary-structure prediction of the region surrounding Phe-360 suggests that this mutation should not produce any significant structural change . The purified mutant acylase was able to hydrolyse adipyl-, glutaryl-, valeryl-, caproyl-, heptanoyl- and phenoxyacetyl-L-leucine at pH 5 with greater efficiency than the wild-type enzyme . However, the mutant enzyme was not able to hydrolyse glutaryl-7-aminocephalosporanic acid and had lost 90% and 50% of activity on penicillin G and phenylacetyl-L-leucine respectively . Nevertheless, mutant PA retained its original activity on 6-nitro-3-phenylacetamidobenzoate and p-nitrophenylphenylacetate, suggesting that the binding specificity of PA by the acyl and amine moieties of the substrate are not independent phenomena . The small differences observed between the c.d . spectra of the mutant enzyme recorded at pH 5 and 8 suggest the existence of different conformational states at the two pH values, but these differences were indistinguishable from those observed in the native enzyme and cannot be correlated with the shift in substrate specificity . Our results demonstrate that it is possible to change the specificity of PA by laboratory evolution and use it to identify the amino acids involved in substrate recognition . However, the synchronous participation of the alpha- and beta-subunits in the complex induced-fit-like mechanism of acylases suggests that, to obtain new enzymes for industrial application, the selection pressure should be specifically designed for the compound of interest.

Rev Invest Clin, 1994 Nov-Dec, 46(6), 431 - 6
{Prevalence of antitreponemal antibodies in 3,098 female prostitutes in Mexico City}; Calderon-Jaimes E et al.; This paper describes a serological survey applied to 3098 female commercial sex workers, in order to determine the prevalence of syphilis . The women attend regularly an AIDS orientation center sponsored by CONASIDA in Mexico City . The laboratory tests included the rapid plasma reagin assay (presumptive analysis) and the fluorescent treponemal antibody-absorption technique (confirmatory test) . No primary syphilis cases were detected and the prevalence of latent asymptomatic syphilis was 8.2% (255/3098) . The sensitivity and specificity of the presumptive test compared to the confirmatory test were 74% and 98% respectively, and the positive predictive value was 77% and the negative predictive value 98% . All seropositive women received the standard penicillin treatment for syphilis . Considerations of importance are offered regarding interpretation and usefulness of this kind of research.

Clin Infect Dis, 1994 Nov, 19(5), 958 - 60
Transdiaphragmatic Actinobacillus actinomycetemcomitans infection: case report; Chao CL et al.; To our knowledge, we report the first case of transdiaphragmatic Actinobacillus actinomycetemcomitans infection in which the patient presented with an abdominal tumor . The clinical manifestation of this infection was similar to that of Actinomyces israelii infection and was initially misinterpreted as a malignancy . The actual diagnosis was made following prolonged culture of the biopsy specimen of the involved tissue . The pathogen was susceptible to penicillin, ampicillin, tetracycline, cephalosporins, metronidazole, aminoglycosides, and quinolones . The patient was treated with a combination of amoxicillin and norfloxacin, and 3 months later his condition had clinically improved.

Psychiatr Pol, 1994 Nov-Dec, 28(6), 677 - 85
{Acute non-allergic reaction after administration of penicillin as a factor in the occurrence of neurotic symptoms}; Magiera P et al.; The effect of a acute non-allergic reaction occurring after injection of procaine penicillin on the occurrence of different neurotic symptoms is a subject of the paper . 31 clinical cases, in which during the penicillin treatment the said reaction took place, were analysed . It has been found that the most often found consequence of that treatment is conversive neurosis, and subsequently the hypochondriac syndrome . On an average an acute non-allergic reaction occurred after the sixth injection . In 94% of the patients the neurotic symptoms appeared immediately after the described reaction . A positive correlation between the patient's age and an intensity of the converse symptoms was found . The Hoigne'a syndrome was a strong mental trauma, and was treated as an allergic shock for all of the patients . The patients were afraid of the next injection and they all refused to give permission for the continuation of such treatment . Neurotic syndromes related to Hoigne's syndrome turned out to be prolonged with a tendency for relapses, and low susceptibility to different methods of treatment . The mechanism of non-allergic acute reaction after procaine penicillin and ways of its prevention are also discussed.

Anal Chem, 1994 Nov 1, 66(21), 3651 - 8
Determination of beta-lactam residues in milk using perfusive-particle liquid chromatography combined with ultrasonic nebulization electrospray mass spectrometry; Straub R et al.; The introduced electrospray (ESP) technique combined with quadrupole mass spectrometry (MS) was applied for the trace residue detection (10 ppb) of commonly administered beta-lactam antibiotics in bovine milk . Because of the widespread use of penicillin G, ampicillin, amoxicillin, cephapirin, cloxacillin, and ceftiofur in veterinary medicine, these six popular drugs were chosen to develop a fast and reliable microcolumn liquid chromatographic (micro-LC) separation method for residue-containing milk extracts . Furthermore, the analytes were selected to test the chromatographic behavior of a novel stationary phase, a perfusive-particle column packed with derivatized porous polystyrene divinylbenzene . The effects of mobile phase additives on separation and ESP ionization efficiency were investigated . The ionization of the eluted analytes took place either in a conventional ESP interface with a capillary shield allowing flow rates up to 40 microL/min or in the latest model of the ultrasonic nebulization ESP interface . The perfusive-particle column, although not optimized for the separation of small molecules, exhibited sufficient resolution of the antibiotics for its routine usage, especially when considering the remarkable time-saving advantage compared with ordinary reversed phase micro-LC columns . The application of the novel ultrasonic nebulization interface lowered detection limits and improved the stability of the signals over a much wider flow rate range than possible for ionization with the ESP system equipped with the conventional needle.

J Antimicrob Chemother, 1994 Nov, 34(5), 813 - 7
Aspoxicillin versus piperacillin in severe abdominal infections--a comparative phase III study; Scheinin H et al.; We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection . Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess . Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing . The efficacy rates were similar in the two study groups . Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS) . The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs . Both drugs were generally well tolerated and no serious drug-related adverse events were noted . However, five patients died because of their illness and one patient had a fatal myocardial infarction . In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.

J Med Chem, 1994 Oct 28, 37(22), 3707 - 16
Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors: heterocyclic ring systems containing P1' and P2' substituents; Kitchin J et al.; As an extension of our earlier work based upon a single penicillin-derived thiazolidine moiety we have found that the decahydroisoquinoline grouping, also present in Ro 31-8959, is an effective replacement for one of the thiazolidine units in C2 symmetric penicillin-derived dimers . Reaction of racemic epoxide 6 with {3S-{3 alpha, 4a alpha, 8a alpha}}-decahydro-N-(1,1-dimethylethyl)-3- isoquinolinecarboxamide gave diasteroisomers 34a and 34b . The stereochemistry of the hydroxyl grouping of 34a was determined to be (S) . Reaction of the amines derived from 34a and 34b with thiazolidine 8a gave 50 and 51, respectively . Compound 50 was a potent inhibitor of HIV proteinase (IC50 = 23 nM) with antiviral activity against HIV-1 in vitro (EC50 C8166 cells = 50 nM) . However, a poor pharmacokinetic profile in the dog for compound 50 and its analogues, in keeping with earlier studies on penicillin-derived dimers in three species, precluded their development as potential antivirals.

Biochem J, 1994 Oct 15, 303 ( Pt 2), 357 - 62
Site-directed mutagenesis of proposed active-site residues of penicillin-binding protein 5 from Escherichia coli; van der Linden MP et al.; Alignment of the amino acid sequence of penicillin-binding protein 5 (PBP5) with the sequences of other members of the family of active-site-serine penicillin-interacting enzymes predicted the residues playing a role in the catalytic mechanism of PBP5 . Apart from the active-site (Ser44), Lys47, Ser110-Gly-Asn, Asp175 and Lys213-Thr-Gly were identified as the residues making up the conserved boxes of this protein family . To determine the role of these residues, they were replaced using site-directed mutagenesis . The mutant proteins were assayed for their penicillin-binding capacity and DD-carboxypeptidase activity . The Ser44Cys and the Ser44Gly mutants showed a complete loss of both penicillin-binding capacity and DD-carboxypeptidase activity . The Lys47Arg mutant also lost its DD-carboxypeptidase activity but was able to bind and hydrolyse penicillin, albeit at a considerably reduced rate . Mutants in the Ser110-Gly-Asn fingerprint were affected in both acylation and deacylation upon reaction with penicillin and lost their DD-carboxypeptidase activity with the exception of Asn112Ser and Asn112Thr . The Asp175Asn mutant showed wild-type penicillin-binding but a complete loss of DD-carboxypeptidase activity . Mutants of Lys213 lost both penicillin-binding and DD-carboxypeptidase activity except for Lys213His, which still bound penicillin with a k+2/K' of 0.2% of the wild-type value . Mutation of His216 and Thr217 also had a strong effect on DD-carboxypeptidase activity . Thr217Ser and Thr217Ala showed augmented hydrolysis rates for the penicillin acyl-enzyme . This study reveals the residues in the conserved fingerprints to be very important for both DD-carboxypeptidase activity and penicillin-binding, and confirms them to play crucial roles in catalysis.

Hosp Pract (Off Ed), 1994 Oct 15, 29(10), 31 - 6; discussion 36-7
Combating drug-resistant pneumococcal infections; Sanford JB; Penicillin-resistant pneumococcal strains continue to spread . Some strains are also resistant to other antibiotics, including the cephalosporins . Better utilization of the 23-valent pneumococcal vaccine, which covers the serotypes responsible for 90% of pneumococcal infections, is an important step in combating resistance.

J Med Screen, 1994 Oct, 1(4), 229 - 32
Neonatal screening for sickle cell disease in a metropolitan university hospital: efficacy and problems; Ballas SK et al.; OBJECTIVE: To determine the effectiveness of a screening programme to identify infants with sickle cell anaemia . SETTING: A metropolitan university hospital . METHOD: 4845 (73.3%) newborn cord blood samples from 6271 infants born in the Thomas Jefferson University Hospital over a two year period were tested for the presence of haemoglobinopathies . The patient group comprised approximately 44% white Americans and 51% African Americans . Diagnoses of haemoglobinopathies were established by cellulose acetate (pH 8.6) and citrate agar (pH 6.2) electrophoresis, and thin layer isoelectric focusing . RESULTS: 17 African American infants were suspected of having sickle cell anaemia and their families were notified and called for retesting to confirm the diagnosis . Fourteen of these families responded; retesting confirmed the diagnosis of sickle cell anaemia in 12 (86%), and the remaining two (14%) had sickle cell trait . The other three families never responded and all efforts to reach them were unsuccessful so the diagnosis could not be confirmed . The infants for whom the diagnosis of sickle cell anaemia was confirmed were treated prophylactically with penicillin and enrolled in sickle cell programmes . Of 398 infants with an abnormal haemoglobin (Hb), 170 (3.5% of all infants tested) showed sickle trait, 63 (1.3%) showed Hb C trait, and 165 samples (3.4%) showed Hb Bart's . Letters of notification were sent to those families whose infants had sickle trait or Hb C trait . Thirty three (16%) families responded and asked for additional information, counselling, or testing of other family members . Three of these families (about 0.1% of all white subjects tested) were white subjects of Italian, English, and Polish ancestry, and all of their infants had sickle trait . Additional testing on other family members showed that one black parent had Hb SC disease that had not previously been diagnosed as the subject was asymptomatic . CONCLUSIONS: A screening programme for newborns in a metropolitan hospital (a) was effective in identifying and treating infants with sickle cell anaemia with prophylactic penicillin, (b) was associated with difficulties in tracking infants and their families in about 30% of suspected cases of sickle cell disease, (c) found that sickle trait is not uncommon in white subjects, and (d) found that "silent" sickle cell disorders to occur among American black subjects.

HNO, 1994 Oct, 42(10), 624 - 8
{Current aspects in diagnosis and therapy of pediatric facial paralysis}; Wolf SR et al.; Between 1986 and 1992, 60 children with facial nerve palsy (FNP) were examined at the ORL hospital at Erlangen-Nuremberg University . By using blood and cerebrospinal fluid (CSF)-serological tests acute infection with Borrelia burgdorferi (B.b.) could be proved in 16 of 40 children (40%) whose pareses could not be clarified etiologically at first examination . Whereas all idiopathic FNP patients (22) had normal CSF-results, more than half of the B.b.-infected children showed pathological findings, with pleocytosis indicating meningitis . These findings demonstrated that lumbar puncture should be performed in children with FNP of unclear etiology, particularly in cases with positive borreliosis blood serology . The children with borreliosis received penicillin G or ceftriaxone intravenously for at least 14 days and patients with idiopathic FNP were treated with cortisone either orally alone or intravenously in combination with pentoxifylline and hydroxyethylstarch . The outcome in 95% of the patients showed that complete recovery was similar in borreliosis and idiopathic FNP irrespective of treatment with cortisone . Overall, 88% of the FNP recovered completely, indicating a favorable prognosis of FNP in children.

Med Clin (Barc), 1994 Oct 1, 103(10), 379 - 82
{Validity of intrathecal secretion formulas of IgG in the follow-up of the response to neurosyphilis treatment}; Marin J et al.; The different formulas on intrathecal secretion of IgG were evaluated in patients with active neurosyphillis (NS) who did not have HIV infection with the aim of knowing their usefulness and sensitivity in the follow up of response to treatment . Five HIV negative patients with defined criteria of active NS were analyzed . The QAib ratio (albumin LCR/serum x 1,000) and Tourtellotte, Schuller and Reiber formulas of intrathecal secretion and the Link's index were studied prior to and at 15 days and three months following treatment with high intravenous doses of penicillin G over 12 days . A decrease in the QAlb ratio and all the formulas of intrathecal secretion of IgG was observed after treatment . The mean decrease was statistically significant on the third month after treatment for the Tourtellotte formula (116.6 +/- 44 mg/dl in basal control, 60.7 +/- 38 mg/dl at 15 days and 46.5 +/- 59 mg/dl at three months) (p < 0.05) . The same evolutive pattern was not observed with the Link's index 1.75 +/- 9 mg/dl in basal control, 1.16 +/- 5 mg/dl at 15 days and 1.79 +/- 1 mg/dl at 3 months) in this series . The formulas of intrathecal secretion of IgG are useful to evaluate the response to treatment of patients with active neurosyphilis . The Tourtellotte formula was shown to be better than the Link index in this evaluation.

Mo Med, 1994 Oct, 91(10), 630 - 5
Congenital syphilis: a reminder about the return of an old scourge; Dehner LP et al.; Congenital syphilis had almost become a forgotten disease with the advent of maternal prenatal serology and penicillin therapy for infected mothers . From the 1950s into the mid-1980s, cases of congenital syphilis steadily declined to only 688 cases in the United States in 1988; however, the number of cases increased to 2,841 by 1990 . The heralding event occurred between 1981 and 1989 with a 34% increase nationally in the incidence of primary and secondary syphilis . A peak in the number of cases of congenital syphilis was attained in 1992 in the country at large, but in 1993 in the State of Missouri, there were almost three times as many cases as were reported in 1992 . Physicians, particularly those who practice in the metropolitan areas of the state, should be alert to the clinical profile of prospective mothers who may have primary or secondary syphilis.

J Parasitol, 1994 Oct, 80(5), 826 - 9
In vitro survival and retention of infectivity of Plasmodium yoelii sporozoites over extended periods of time; Siu NF et al.; The ability to maintain sporozoites in vitro should render the biological mechanism of sporozoite infectivity amenable to experimental analysis . With this in mind, Plasmodium yoelii Py17X(NL) clone 1.1 sporozoites were incubated at 4, 24, or 37 C for 0, 8, or 24 hr in tissue culture medium M199 with 5% normal mouse serum and penicillin-streptomycin . BALB/c mice were challenged intravenously with 5,000 in vitro-incubated sporozoites and then evaluated daily for parasitemia beginning on day 3 postinoculation . Sporozoites held at 24 C remained infective up to 24 hr unlike sporozoites incubated at 4 and 37 C . We observed 100% infection in mice challenged with a minimum of 200, 40, and 1,000 sporozoites that were in vitro incubated at 24 C at times 0, 24, and 36 hr, respectively . Infectivity was also maintained for 24 hr at 24 C in RPMI-1640 with 5% normal mouse serum and penicillin-streptomycin . Injection of 5,000 or 1,000 in vitro-cultured sporozoites gave 100% infection in BALB/c mice . We have demonstrated that P . yoelii sporozoites can survive in culture for extended periods of time with no apparent adverse effects on sporozoite infectivity.

J Bacteriol, 1994 Oct, 176(19), 6088 - 99
Isolation of the outer membranes from Treponema pallidum and Treponema vincentii; Blanco DR et al.; The outer membranes from Treponema pallidum subsp . pallidum and Treponema vincentii were isolated by a novel method . Purified outer membranes from T . pallidum and T . vincentii following sucrose gradient centrifugation banded at 7 and 31% (wt/wt) sucrose, respectively . Freeze fracture electron microscopy of purified membrane vesicles from T . pallidum and T . vincentii revealed an extremely low density of protein particles; the particle density of T . pallidum was approximately six times less than that of T . vincentii . The great majority of T . vincentii lipopolysaccharide was found in the outer membrane preparation . The T . vincentii outer membrane also contained proteins of 55 and 65 kDa . 125I-penicillin V labeling demonstrated that t . pallidum penicillin-binding proteins were found exclusively with the protoplasmic cylinders and were not detectable with purified outer membrane material, indicating the absence of inner membrane contamination . Isolated T . pallidum outer membrane was devoid of the 19-kDa 4D protein and the normally abundant 47-kDa lipoprotein known to be associated with the cytoplasmic membrane; only trace amounts of the periplasmic endoflagella were detected . Proteins associated with the T . pallidum outer membrane were identified by one- and two-dimensional electrophoretic analysis using gold staining and immunoblotting . Small amounts of strongly antigenic 17- and 45-kDa proteins were detected and shown to correspond to previously identified lipoproteins which are found principally with the cytoplasmic membrane . Less antigenic proteins of 65, 31 (acidic pI), 31 (basic pI), and 28 kDa were identified . Compared with whole-organism preparations, the 65- and the more basic 31-kDa proteins were found to be highly enriched in the outer membrane preparation, indicating that they may represent the T . pallidum rare outer membrane proteins . Reconstitution of solubilized T . pallidum outer membrane into lipid bilayer membranes revealed porin activity with two estimated channel diameters of 0.35 and 0.68 nm based on the measured single-channel conductances in 1 M KCl of 0.40 and 0.76 nS, respectively.

Indian J Physiol Pharmacol, 1994 Oct, 38(4), 303 - 5
Cross reactivity of cephalosporins with penicillin; Dhar HL et al.; Cross antigenicity of cephalosporins with penicillin has been studied experimentally and also by using serum from penicillin sensitive individuals . Definite hypersensitivity reaction was observed in all the animals sensitised with cephalosporins and challenged with penicillin except in rats . Cephalosporins could elicit reaction in tissues sensitised passively with serum obtained from penicillin sensitive individuals.

Clin Investig, 1994 Oct, 72(10), 794 - 8
Amanita poisoning during the second trimester of pregnancy . A case report and a review of the literature; Nagy I et al.; Amanita phalloides-type mushroom poisoning is well recognized as causing acute liver injury and often death . Less is known, however, of whether maternal Amanita poisoning is associated with fetal damage or not . In August 1991 four members of a family were hospitalized with food intoxication caused by Amanita phalloides and Amanita verna . One of them died from hepatic and renal failure . The survivors included a 26-year-old woman in the 23rd week of pregnancy . Her clinical symptoms and blood chemistry data (lowest prothrombin activity 23%) indicated intoxication of medium severity . The management consisted of i.v . hydration, forced diuresis, and administration of silibinin, high-dose penicillin, thioctic acid, hydrocortisone, vitamin K, and fresh frozen plasma . Sonographic and obstetric controls failed to show any fetal abnormalities in the acute phase of poisoning . In the 38th week of pregnancy she gave birth to a healthy baby, who has subsequently undergone an undisturbed development . This observation indicated that severe fetal damage did not occur in maternal Amanita poisoning in the second trimester of pregnancy . Thus, at least from the second trimester on, maternal Amanita poisoning is not necessarily an indication for induced abortion.

Nippon Ronen Igakkai Zasshi, 1994 Oct, 31(10), 811 - 4
{A case of successful antisyphilitic treatment for a patient with general paresis}; Hirasawa H et al.; A 59-year-old male patient with general paresis was hospitalized because of personality changes and memory disturbances without any neurological deficits . His Mini Mental State score was 11, and his total IQ on the WAIS-R was 56 . TPHA titers in serum and the CSF were over 40960x and 640x respectively . Both the white blood cell count as well as total protein were found to be increased in the CSF and FTA-ABS in the CSF was positive . The patient was treated with penicillin, one million units per day intramuscularly for 14 days, and four million units per day intravenously for 10 days . The abnormal findings in the CSF, his unstable mood and agitation improved, as well as his scores on the Mini Mental State (17) and total IQ (74), and the patient was able to once again function socially . This case emphasizes the importance of early diagnosis and treatment of general paresis.

J Toxicol Sci, 1994 Oct, 19 Suppl 2, 249 - 62
{Antigenicity tests of tazobactam/piperacillin, tazobactam and piperacillin}; Takemoto M et al.; The antigenicity tests of Tazobactam/piperacillin (TAZ/PIPC), tazobactam (TAZ:beta-lactamase inhibitor) and piperacillin (PIPC:penicillin antibiotic) were performed in mice and guinea pigs . The following results were obtained . 1 . TAZ/PIPC, TAZ or PIPC had no immunogenicity and allergenicity in either passive cutaneous anaphylaxis (PCA) test using BALB/c and C3H/He mice or in PCA test using guinea pigs . 2 . Guinea pigs sensitized with TAZ/PIPC, TAZ or PIPC showed no anaphylactic symptoms in active systemic anaphylaxis (ASA) test . 3 . Guinea pig PCA tests using protein conjugates as sensitizing and challenging antigens showed positive reactions . Immunological cross-reactivity tests were performed by using these conjugates in guinea pig PCA reaction . Results showed that TAZ/PIPC and PIPC cross-reacted with penicillin G (PCG) and ampicillin (ABPC), but not with cephalothin (CET) and cephmetazol (CMZ) . TAZ did not cross-react with PCG, ABPC, CET or CMZ . 4 . From the results of the passive hemagglutination (PHA) test, no antibody against TAZ/PIPC, TAZ or PIPC was detected . 5 . In direct Coombs' test using human blood, TAZ/PIPC, TAZ, PCG and CET showed positive reactions at 20-80, 5-20, 80 and 10-20 mg/ml, respectively . 6 . The results of a test on in vitro covalent binding activity with human serum albumin indicated that the order of binding potency was CET > CMZ > ABPC > PCG = PIPC > TAZ under the physiological condition (pH 7.2-7.4), and was CMZ > CET > ABPC > PIPC > TAZ > PCG under the alkaline condition (pH 10.0-10.5), respectively.

J Trop Pediatr, 1994 Oct, 40(5), 301 - 4
Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin + procaine penicillin G in the treatment of childhood pneumonia; Sidal M et al.; This study, which aimed to assess the results of three different regimens in the treatment of pneumonia, was carried out at the Pediatric Outpatient Department of Capa Children's Hospital in Istanbul on 151 patients aged between 4 months and 14 years . The first group (n = 46) received co-trimoxazole orally for 10 days and the second group (n = 63) procaine penicillin G in intramuscularly for 10 days . Benzathin penicillin G combined with procaine penicillin G was given to the third group (n = 42) as a single dose intramuscularly . While the best results were obtained with penicillin procaine G, no statistically significant difference was found between this regimen and co-trimoxazole therapy (chi 2 = 0.305023 P = 0.5) . We suggest that co-trimoxazole is easy to administer and cost effective in the ambulatory treatment of pneumonia in children.

Nippon Ika Daigaku Zasshi, 1994 Oct, 61(5), 389 - 404
{Use of patch-scratch tests to determine penicillin and cephem allergies}; Egawa Y; The drug eruptions caused by penicillins and cephems and the patch-scratch test reactions to these drugs are discussed herein . Five hundred eighty two patients were diagnosed with drug eruption as a result of patch-scratch tests, history, gurgle tests or challenge tests in the 22 years from 1971 to 1992 in our department . Of these cases 53.8% were caused by penicillins, and 29.9% by cephems . The number of cases of allergic reactions to both, especially cephems has been increasing steadily over the last 10 years . Patch-scratch tests were performed on 382 patients among 385 patients with drug eruption caused by penicillin or cephem out of the 582 patients above mentioned . Among these patients, the patch-scratch test positive rate for penicillins and cephems was 84%, suggesting that the patch-scratch test is useful for identifying penicillin and cephem allergies . Patch-scratch tests for our antibiotics series were performed on 1256 patients with drug eruption or contact dermatitis caused by some allergens, whether the allergens were penicillins or cephems, or neither, 29.5% of these showed positive reactions to penicillins and 12.7% to cephems . Among these patients, patch-scratch tests for our penicillin and cephem series were also performed on 81 patients, 88.9% of whom showed positive reactions to penicillins and 59.3% to cephems . The highest incidence of positive reactions, 77.8%, occurred with wide spectrum semisynthetic penicillins . Of this group, ampicillin had the highest incidence at 58% . In 32 cases, the allergen could be detected . As to the clinical types of these cases, maculopapular eruptions and erythroderma showed the highest incidence . Cross reactions also occurred within the same group, most being for wide spectrum semisynthetic penicillin . The optimum concentration of each allergen used in the patch-scratch tests was evaluated on the basis of the relationship between the concentration of the allergens and the results of the patch-scratch tests . The results were 20w/w% in ABPC, AMPC, SBPC, CER, CMZ, CZX and LMOX, 10 w/w% in PCG and CBPC, 5w/w% in CMD . Drug lymphocytic stimulation tests were performed in 12 cases, with 15 drugs producing positive patch-scratch test reactions . Only 3 drugs showed positive reactions, suggesting that this test is unreliable.

Physiol Behav, 1994 Oct, 56(4), 715 - 21
Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in rats; De Riu PL et al.; The influence of the cerebellum and mesencephalon on epileptic bulbar discharge induced by topical application of penicillin-G on the floor of the IVth ventricle was analyzed in rats . Bulbar multiunit activity was recorded at different depths . The animals were divided into two main groups: totally cerebellectomized rats (Group I) and lobus anterior cerebellectomized rats (Group II) . Each main group was further subdivided into two subgroups: animals with intact mesencephalon and animals with transected mesencephalon . In Group I: the total cerebellectomy, in intact mesencephalic rats (first subgroup) induced a sudden disappearance of bulbar epileptic discharge . The mid-collicular transection (second subgroup) produced the immediate disappearance of bulbar paroxysms and the total cerebellectomy, subsequently performed, further decreased the spontaneous firing rate . In Group II: (first subgroup) the lobus anterior ablation in rats with intact mesencephalon, significantly enhanced the paroxysmal discharge . In the second subgroup, where the midcollicular transection had provoked the disappearance of bulbar paroxysms, the lobus anterior ablation induced the immediate reappearance of the paroxysmal activity . The penicillin-G epileptogenic activity showed a different intensity at different depths in the bulb with a maximum intensity at the level of the vestibular nuclei . In conclusion, the present study shows that both the mesencephalon and the cerebellum have a facilitating influence on bulbar epileptic discharge induced by the topical application of the GABA antagonist . However, not all the cerebellum has a facilitating effect, because the anterior lobus was found to have an inhibitory influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Appl Microbiol Biotechnol, 1994 Oct, 42(1), 85 - 91
Periplasmic aggregation limits the proteolytic maturation of the Escherichia coli penicillin G amidase precursor polypeptide; Scherrer S et al.; The Escherichia coli penicillin G amidase (PGA), which is a key enzyme in the production of penicillin G derivatives is generated from a precursor polypeptide by an unusual internal maturation process . We observed the accumulation of the PGA precursor polypeptide in the insoluble material recovered after sonication of recombinant E . coli JM109 cells grown at 26 degrees C . The aggregated nature of the accumulated molecules was demonstrated using detergents and chaotropic agents in solubilization assays . The periplasmic location of the aggregates was shown by trypsin-accessibility experiments performed on the spheroplast fraction . Finally, we showed that addition of sucrose or glycerol in the medium strongly reduces this periplasmic aggregation and as a consequence PGA production is substantially increased . Thus, periplasmic aggregation of the PGA precursor polypeptide limits PGA production by recombinant E . coli and this limitation can be overcome by addition in the medium of a non-metabolizable sugar, such as sucrose, or of glycerol.

Enzyme Microb Technol, 1994 Oct, 16(10), 895 - 903
Exponentially fed-batch cultures as an alternative to chemostats: the case of penicillin acylase production by recombinant E . coli; Ramirez OT et al.; Exponentially fed-batch cultures (EFBCs), fed with medium containing a highly concentrated carbon source, are commonly employed for attainment of high cell densities . However, large variations in environmental conditions occur, and quasi-steady-state is usually achieved only for the limiting substrate concentration, restricting the use of such cultures in kinetic characterization studies . In this work we report the production of recombinant penicillin acylase (PA) in EFBC of an E . coli JM101 transformed with the pPA102 plasmid, which includes the PA gene under regulation of the lacZ gene promoter and using isopropyl-beta-thio-galactopyranoside (IPTG) as inducer . The culture was fed with nonconcentrated complete medium, resulting in the attainment of quasi-steady-state conditions not only in substrate concentration, but also in cell concentration, and in the specific rates of growth, product production, and substrate consumption . Similar transient behavior was observed between EFBC and chemostat results . At quasi-steady-state, the dilution rate in the EFBC equaled the growth rate . Specific PA production rate during the fed-batch phase remained relatively constant at each dilution rate and followed typical Luedeking-Piret kinetics, with growth-associated and non-growth-associated constants of 142 U gDCW-1 and 7.2 U gDCW-1 h-1, respectively . Specific glucose consumption rate linearly increased from 0.025 to 0.6 g gDCW-1 h-1 as the dilution rate increased from 0.01 to 0.35 h-1 . The maximum specific PA activity increased with decreasing dilution rate, reaching its highest value of 2.0 U mg-1 at a dilution rate of 0.01 h-1, the lowest dilution tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene, 1994 Sep 15, 147(1), 41 - 6
Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis; Aidoo KA et al.; During the purification of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) from Streptomyces clavuligerus, a small protein (CLA) involved in clavulanic acid production co-purified with ACVS . A 24-mer mixed-DNA probe based on the N-terminal amino-acid sequence of CLA was used to isolate the corresponding gene (cla), located near one end of the known cluster of penicillin and cephamycin biosynthetic genes, 5.7 kb downstream from the pcbC gene which encodes isopenicillin-N synthase . The sequence of cla would encode a protein of 313 aa with a high degree of similarity to amidinohydrolase enzymes . The cla gene is located immediately upstream from the previously described clavaminate synthase 2-encoding gene (cs2), and cla homologs were only present in streptomycetes which produced clavam compounds . Replacement of cla with a disrupted copy of the gene blocked the production of clavulanic acid in starch asparagine medium (SA).

Biochem J, 1994 Sep 15, 302 ( Pt 3), 851 - 6
Relative specificities of a series of beta-lactam-recognizing enzymes towards the side-chains of penicillins and of acyclic thioldepsipeptides; Xu Y et al.; In an attempt to understand more of the subtle differences between bacterial beta-lactamases and DD-peptidases, comparisons have been made between the specificities of these enzymes towards the phenylacetyl side chain, generally thought to be favoured by beta-lactamases, and the NN'-diacetyl-L-lysyl side chain, widely employed in low-molecular-mass substrates of DD-peptidases . These comparisons were carried out with both a penicillin and an acyclic thioldepsipeptide reaction nucleus and employing a range of both beta-lactamases and DD-peptidases . Rather contrary to general expectations, a general preference for reaction of both groups of enzymes with penicillins rather than thioldepsipeptides was observed and for the phenylacetyl rather than the NN'-diacetyl-L-lysyl side chain . Quantitative comparisons suggested that the side chains of penicillins may be bound in relatively similar sites in all of the enzymes whereas the side chains of thioldepsipeptides are more heterogeneously bound, both with respect to each other and to the comparable side chains of penicillins.

Am J Gastroenterol, 1994 Sep, 89(9), 1569 - 72
Actinomyces infection of a cytomegalovirus esophageal ulcer in two patients with acquired immunodeficiency syndrome; Poles MA et al.; Esophageal disease is a significant cause of morbidity among patients with the acquired immunodeficiency syndrome (AIDS) . Many organisms have been implicated in the pathogenesis of dysphagia and odynophagia . We describe a unique presentation of actinomyces esophageal infection in two homosexual male patients with AIDS and biopsy proven CMV esophagitis . After failure of esophagitis to resolve with ganciclovir or foscarnet therapy, the patients underwent repeat endoscopy and were subsequently found to have a secondary infection of the ulcers by Actinomyces . Treatment with intravenous penicillin G resulted in symptomatic and histopathological resolution of esophageal disease . This appears to be the first report of Actinomyces infection of esophageal ulcers in AIDS patients, possibly a commonly overlooked diagnosis.

Am J Med Sci, 1994 Sep, 308(3), 184 - 5
Case report: anaerobic meningitis caused by Peptostreptococcus magnus after head and neck surgery; Brown MA et al.; Although anaerobic bacterial meningitis is uncommon, patients subjected to resection of head and neck malignancy appear at special risk . In this article, the authors report on a 72-year-old man in whom meningitis developed after extensive resection of the right sinuses for squamous cell carcinoma; initial treatment consisted of intravenous vancomycin and ceftazidime . Intravenous penicillin G was added after the fortuitous early finding of intracellular cocci in Wright-Giemsa stained cerebral spinal fluid submitted for cell count . Cerebral spinal fluid cultures then grew out a pure culture of Peptostreptococcus magnus . The patient had a complete recovery, without neurologic sequelae, recurrence of malignancy, or evidence of infection . Appropriate handling of cerebral spinal fluid specimens is crucial to ensure the correct diagnosis when anaerobic organisms are suspected.

J Pediatr, 1994 Sep, 125(3), 471 - 5
Treatment of asymptomatic congenital syphilis: benzathine versus procaine penicillin G therapy; Paryani SG et al.; We compared the efficacy of two treatment regimens for asymptomatic congenital syphilis . Between June 1989 and July 1991, we prospectively and randomly assigned 169 patients to receive either one dose of benzathine penicillin G or procaine penicillin G for 10 days . There were no significant differences between the treatment groups in regard to birth weight, sex, race, gestational age, Apgar scores, infant or maternal rapid plasma reagin (RPR) titers, fluorescent treponemal IgM antibody, or maternal treatment . Patients were examined at 2 to 3, 6, and 12 months after treatment; treatment failure was defined as clinical signs or persistent laboratory evidence of congenital syphilis . Nine patients were removed from the study during the neonatal period, eight were lost to follow-up, and 152 patients were examined 2 to 3 months or more after treatment . Among these 152 patients, none had clinical evidence of congenital syphilis at follow-up, and all the patients tested at 2 to 3 months after treatment (68 in the benzathine penicillin G group and 61 in the procaine penicillin G group) had at least a fourfold decrease in RPR titers . The RPR became nonreactive in all but three of the infants (two in the procaine penicillin G group and one in the benzathine penicillin G group; all three were 2 to 3 months of age when last tested) . We conclude that treatment failure did not occur with either regimen and that there was no significant difference in outcome between the two groups.

Psychiatr Pol, 1994 Sep-Oct, 28(5), 613 - 25
{Procaine kindling in acute non-allergic reaction to procaine penicillin G}; Araszkiewicz A et al.; On the basis of the analysis of acute nonallergic reaction to a course of procaine penicillin G, the authors have stated that symptoms of this reaction result from the irritation of temporal limbic structures . The authors think that it is connected with procaine kindling mechanism, the procaine component of the drug.

J Laryngol Otol, 1994 Sep, 108(9), 801 - 3
Cervicofacial actinomycosis presenting as acute upper respiratory tract obstruction; Balatsouras DG et al.; An unusual case of cervicofacial actinomycosis presenting as acute upper airway obstruction and demanding urgent tracheostomy is reported . Diagnosis was established by microscopic examination of the pus and culture of Actinomyces israelii . Repeated surgical drainage of the purulent foci and prolonged treatment with penicillin obtained resolution of the disease . Clinicians dealing with acute head and neck swellings should always consider actinomycosis as a possible diagnosis.

Indian J Med Res, 1994 Sep, 100, 135 - 9
Effect of cerebellar stimulation on EEG power spectra in the acute model of epilepsy; Culic M et al.; Experiments were performed to investigate the effects of cerebellar stimulation on epilepsy induced by parenteral administration of penicillin, in rats without or with the lesion of sensorimotor cortex . There were no differences in the EEG activity of the same experimental animal after the first and subsequent penicillin treatments (at least 7 days later) . The electrical stimulation (duration of 5-10 min) of the lateral cerebellar nucleus was applied repetitively 135-315 min after penicillin administration, when the EEG power spectra markedly increased . The cerebellar stimulation evoked the decrease of the mean total EEG power spectra, but the effects were temporary . The EEG power spectra were significantly lower (P < 0.05) during the period of 150-330 min after penicillin treatment in experimental sessions with applied cerebellar stimulation in comparison to the experimental sessions without such stimulation . The residual effects (if any) of cerebellar stimulation on the EEG activity in the later period, 345-600 after penicillin treatment were not significant (P > 0.05) . Cerebellar stimulation had the same effect among unlesioned animals and animals with prior cortical lesion in the acute model of epilepsy.

J Antibiot (Tokyo), 1994 Sep, 47(9), 1041 - 51
Synthesis of new sulfonylamido-penicillanic acid sulfones inhibitors of beta-lactamases; Vanwetswinkel S et al.; Three new sulfonylamido-penicillanic acid sulfones have been prepared by reaction of 6-aminopenicillanic esters with the monoester or monoamide derivatives obtained in nucleophilic substitution reactions by alcohol or aniline on the carboxyl chloride function of sulfoacetic dichloride followed by oxidation . These penicillin sulfones are converted to beta-lactamases suicide inhibitors by removal of the C3 ester protecting group . This synthetic strategy can give access to sulfonamidopenam sulfones bearing a variety of 6-amino side chain . These inhibitors inactivate the RTEM beta-lactamase rapidly . The kinetics of inactivation are consistent with the partitioning of an acylenzyme intermediate between two main pathways: regeneration of free enzyme and irreversible inactivation, little transient inactivation is observed . A slow inhibition by the product of enzymatic hydrolysis of the sulfones is also observed.

Eur J Biochem, 1994 Sep 1, 224(2), 597 - 604
Penicillin-binding protein 7/8 of Escherichia coli is a DD-endopeptidase; Romeis T et al.; Penicillin-binding protein 7 (PBP7) and its proteolytic degradation product PBP8 are shown to be soluble proteins, which can be set free from whole cells of Escherichia coli by an osmotic shock . The proteins are loosely associated with the membranes and are totally released into the supernatant in the presence of 1 M NaCl . Partial purification of PBP8 was accomplished by hydroxyapatite, heparin-Sepharose and MonoS chromatography . Murein meso-diaminopimelate-D-alanine DD-endopeptidase activity was demonstrated for both PBP7 and PBP8, which specifically hydrolyse the DD-diaminopimelate-alanine bonds in high-molecular-mass murein sacculi but fail to cleave these bonds in isolated dimeric muropeptides . The enzyme is inhibited by the 'penem' beta-lactam antibiotic CGP31608 at a concentration of 0.25 micrograms/ml by 50% . Thus besides PBP4 and the mepA gene product, a third endopeptidase exists in E . coli.

Eur J Biochem, 1994 Sep 1, 224(2), 581 - 7
Structural and functional properties of plasma membranes from the filamentous fungus Penicillium chrysogenum; Hillenga DJ et al.; Functional plasma membranes from the filamentous fungus Penicillium chrysogenum have been isolated with the objective of studying transport processes . The isolation procedure consists of three steps, namely homogenization of cells with a Braun MSK homogenizer, followed by Percoll gradient centrifugation and floatation of membranes in a three-step Nycodenz gradient . This method can be applied to strains which differ significantly in morphology and penicillin-production capacity . Plasma membranes were fused with liposomes containing the beef heart mitochondrial cytochrome-c oxidase . In the presence of reduced cytochrome c, the hybrid membranes maintained a high proton motive force that functions as a driving force for the uptake of the amino acids arginine and valine via distinct transport systems.

Lijec Vjesn, 1994 Sep-Oct, 116(9-10), 255 - 7
{Primary actinomycosis of the liver--case report}; Hozo I et al.; The liver is a rare site of actinomycotic abscess localization . A 36-year-old man admitted to the hospital because of pain under the right costal margin with skin hyperemia and edema in that region is presented . Clinical and laboratory examinations disclosed liver actinomycotic abscess . Surgical drainage was done followed by 8 months of antibiotic (penicillin) therapy . Discussed are the difficulties in diagnostic procedure and the lack of consensus in the therapeutic approach.

Exp Physiol, 1994 Sep, 79(5), 705 - 21
The intracortical neuronal connectivity subserving focal epileptiform activity in rat neocortex; Holmes O; In the anaesthetized rat, regions of the somatosensory cortex have been subpially isolated, leaving intact the cortical blood supply and the connectivity via the white matter . Application of penicillin or strychnine into layer IV of intact cortex resulted in enhancement of amplitude and prolongation of evoked potentials together with the appearance of spontaneous epileptiform discharges . Within a partially isolated region of cortex, spontaneous and evoked potentials occurred as in normal cortex, but application of convulsant drug resulted in no changes in evoked potentials and in no spontaneous spiking . With incisions for which the surface profile measured 0.9 x 0.9 mm, full-depth isolation resulted in interruption of the propensity for epilepsy, whereas half-depth incisions left epileptic manifestations unimpaired . With the surface profile measuring 0.5 x 0.5 mm, half-depth isolation was sufficient to prevent epileptic activity . Results from isolated regions of various geometries and sizes indicated that the ability of cortical neurones to generate epileptic activity depends on the amount of connectivity with surrounding cortex . The propensity of cortex to become epileptic is thus a mass action effect and the 'epileptic neuronal aggregate' is operationally different from anatomically based modular organizations such as thalamo-cortical or cortico-cortical columns . In the small barrel field of the somatosensory cortex, partial isolations that prevented the appearance of spontaneous epileptiform spiking contained many barrels, indicating that a single thalamo-cortical module contains insufficient inherent lateral connectivity to support epileptiform activity . Theoretical considerations indicated that the excitability of a neurone depends both on its monosynaptic connections with other neurones and on the connectivity of these latter with neurones further afield . The interruption of epileptiform activity by partial isolation could be mimicked by a computer model in which connectivity was mediated via short synaptic paths . The model exhibited self-sustaining synchronized neural activity that could be prevented by interruption solely of polysynaptic paths.

Mol Microbiol, 1994 Sep, 13(5), 911 - 7
ppGpp concentration, growth without PBP2 activity, and growth-rate control in Escherichia coli; Joseleau-Petit D et al.; Escherichia coli strains partially induced for the stringent response are resistant to mecillinam, a beta-lactam antibiotic which specifically inactivates penicillin-binding protein 2, the key enzyme determining cell shape . We present evidence that mecillinam resistance occurs whenever the intracellular concentration of the nucleotide ppGpp (guanosine 3'-diphosphate 5'-diphosphate), the effector of the stringent response, exceeds a threshold level . First, the ppGpp concentration was higher in a mecillinam-resistant mutant than in closely related sensitive strains . Second, the ppGpp pool was controlled by means of a plasmid carrying a ptac-relA' gene coding for a hyperactive (p)ppGpp synthetase, RelA'; increasing the ppGpp pool by varying the concentration of lac operon inducer IPTG resulted in a sharp threshold ppGpp concentration, above which cells were mecillinam resistant . Third, the ppGpp pool was increased by using poor media; again, at the lowest growth rate studied, the cells were mecillinam resistant . In all experiments, cells with a ppGpp concentration above 140 pmoles/A600 were mecillinam resistant whereas those with lower concentrations were sensitive . We discuss a possible role for ppGpp as transcriptional activator of cell division genes whose products seem to become limiting in the presence of mecillinam, when cells form large spheres . We confirmed the well-known inverse correlation between growth rate and ppGpp concentration but, surprisingly, for a given growth rate, the ppGpp concentration was lower in poor medium than in richer medium in which RelA' is induced . We conclude that, for E . coli growing in poor media, the concentration of the nucleotide ppGpp is not the major growth rate determinant.

J Biol Chem, 1994 Aug 26, 269(34), 21603 - 7
Specific interaction of penicillin-binding proteins 3 and 7/8 with soluble lytic transglycosylase in Escherichia coli; Romeis T et al.; Soluble lytic transglycosylase 70 (Slt70), one of the better characterized murein hydrolases of Escherichia coli, was covalently bound to CNBr-activated Sepharose and used as a specific tool to screen for proteins showing an affinity for Slt70 . Several proteins were specifically enriched by Slt-Sepharose affinity chromatography . Two of them were identified as the penicillin-binding proteins (PBP)3 and PBP7/8 . Thus, the bifunctional synthase PBP3, specifically involved in septum formation, and PBP7/8, recently shown to be a DD-endopeptidase, bind to Slt70 in vitro . In addition, PBP7/8 was found not only to stabilize but also to stimulate the enzymatic activity of Slt70 by a protein-protein interaction . It is concluded that Slt70, PBP7/8, and PBP3 may form a multienzyme complex in vivo.

Fortschr Med, 1994 Aug 20, 112(22-23), 305 - 7
{Intrauterine device-associated genital actinomycosis . Diagnosis and therapy with reference to five case reports}; Blohmer VJ et al.; Between 1992 and the beginning of 1993, 5 patients attending the gynecological department of the Charite Hospital in Berlin were treated for IUP-associated actinomycosis . The IUP had been used by these women for periods of between five and sixteen years . The primary diagnosis was established on the basis of a histological examination in three cases . In two cases, dysplasias had been diagnosed on the basis of the cytological examination . In one case, the primary diagnosis was suspected by the finding of actinomycetes in the cytological preparation . The treatment of choice is high-dose intravenous penicillin administered over the long term.

FEMS Microbiol Lett, 1994 Aug 15, 121(2), 251 - 6
Site-directed mutagenesis of penicillin-binding protein 3 of Escherichia coli: role of Val-545; Ayala J et al.; Val545 of the Escherichia coli penicillin-binding protein 3 is essential to the acyl transfer mechanism through which the active-site serine 307 is acylated by benzylpenicillin and cephalexin and to the mechanism through which the protein allows rapidly growing cells to divide.

J Mol Biol, 1994 Aug 12, 241(2), 295 - 7
Crystallization and X-ray diffraction study of the Streptomyces K15 penicillin-binding DD-transpeptidase; Englebert S et al.; The 262 amino acid residue long DD-transpeptidase/penicillin-binding protein of Streptomyces K15 has been crystallized at room temperature by using the hanging drop vapour diffusion technique . The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell parameters a = 46.4 A, b = 54.1 A and c = 108.3 A . They contain one protein molecule per asymmetric unit and diffract to about 1.9 A . X-ray data have been collected to 2.0 A from a native crystal . The previously published amino acid sequence of the protein has been corrected at positions 71, 72, 113, 114 and 156.

Prof Care Mother Child, 1994 Aug-Sep, 4(6), 185 - 7
Homoeopathy: 2 . In pregnancy and for the under-fives; Kaplan B; A correctly prescribed constitutional homoeopathic remedy can increase well-being in the preconceptual period . For infertility, orthodox investigations are essential but where tests are normal then homoeopathic treatment of both pariners can maximise their health and may improve the chances of conception . Homoeopathic remedies can be effective for morning sickness and before and during labour . Arnica is helpful for internal and external bruising of both mother and newborn infant . Some problems of breast feeding respond to the homoeopathic remedy Lac-caninum . There is no harm in trying homoeopathy initially for postnatal depression, although severe cases will need orthodox medication . In most conditions there is time to try the holistic stimulus of a homoeopathic remedy to attempt to persuade the body to heal itself . This is a very different principle from the so-called enlightened attitude of some health professionals that there is no harm in trying homoeopathy when orthodox treatment can do no more for the patient . In babies, teething often responds to Chamomilla . The child's susceptibility to certain illnesses, eg recurrent tonsillitis, can be helped by a "whole-patient" homoeopathic remedy, although penicillin may be needed for acute attacks of tonsillitis . In chronic conditions of childhood such as eczema and asthma, homoeopathic doctors believe that correctly chosen remedies are often able to stimulate the body's innate healing ability, leading to an improvement.

J Reprod Fertil, 1994 Aug, 101(3), 657 - 62
Stimulation of progesterone production in bovine luteal cells by co-incubation with bovine blastocyst-stage embryos or trophoblastic vesicles; Thibodeaux JK et al.; A study was conducted to determine whether bovine blastocyst-stage embryos and trophoblastic vesicles stimulate the production of progesterone in bovine luteal cells during incubation in vitro . The effects of co-incubation of these embryos and vesicles with uterine endometrial tissue on progesterone production was also investigated . Bovine small and large luteal cells were obtained on day 12 of the oestrous cycle, dispersed by unit gravity sedimentation and recombined to provide preparations free of accessory cells . Blastocyst-stage embryos were obtained on day 7 and trophoblastic vesicles were obtained from bovine embryos on day 12 . A uterine endometrial tissue sample was obtained from the same cow from which the corpus luteum was taken . Treatment groups were arranged in 24-well plates as follows: luteal cells alone; luteal cells and one trophoblastic vesicle; luteal cells and one blastocyst embryo; luteal cells and a 10 mg uterine endometrial sample; luteal cells, one trophoblastic vesicle and a uterine endometrial sample; and luteal cells, one blastocyst embryo and a uterine endometrial sample . All treatment groups were incubated (at 37 degrees C under 5% CO2) in Ham's F-12 medium supplemented with antibiotics (100 micrograms penicillin ml-1 and 100 U streptomycin ml-1, L-glutamine (0.29 mg ml-1), insulin (5 micrograms ml-1), transferrin (5 micrograms ml-1) and selenium (5 ng ml-1) for 12 h . Samples of the medium were harvested 10 min (basal concentration) and 2, 6 and 12 h after incubation to determine the concentrations of progesterone and prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovasc Res, 1994 Aug, 28(8), 1193 - 8
Streptomycin reverses a large stretch induced increases in {Ca2+}i in isolated guinea pig ventricular myocytes; Gannier F et al.; OBJECTIVE: The aim was to test the hypothesis that in single guinea pig ventricular myocytes a large stretch induced increase in resting calcium was sensitive to the mechanosensitive channel blocker streptomycin . METHODS: Carbon fibres were used to stretch cells loaded with the fluorescent calcium indicator indo-1 . Force, sarcomere length, and internal calcium activity ({Ca2+}i) were measured . RESULTS: In approximately 60% of the cells studied, a stretch which increased sarcomere length by approximately 6% caused a large increase in {Ca2+}i (up to 60% of the size of a {Ca2+}i transient at 0.25 Hz) . When a mixture of antibiotics (streptomycin-penicillin) was used in solutions to isolate and store cells, this phenomenon was never observed (n = 19 cells) . Direct application of physiological saline solution (PSS) could not reverse the increase in {Ca2+}i within 60 s of application (n = 7 cells) . Direct application of penicillin {1000 IU per 50 ml (40 microM)} reversed the increase in {Ca2+}i within 60 s of application in only 3/7 cells . In contrast direct application of the aminoglycoside antibiotic streptomycin (40 microM) rapidly reversed the large increase in {Ca2+}i induced by stretch in each of 13 cells {within 18(SD 10) s of application} . Acute application of 40 microM streptomycin did not modify L-type Ca2+ currents measured under whole cell patch clamp conditions . Measurement of the resting tension--sarcomere length curves in cells stored in solution containing streptomycin and penicillin revealed two populations of cells on the basis of their stiffness . CONCLUSIONS: This stretch induced increase in {Ca2+}i may be associated with stretch activated arrhythmias in the heart . The effects of streptomycin are consistent with its reported inhibitory action on stretch activated channels.

Berl Munch Tierarztl Wochenschr, 1994 Aug, 107(8), 266 - 71
{Blood serum and milk serum levels of sodium benzylpenicillin after intravenous regional antibiosis in surgery of the claw area in cattle}; Stanek C et al.; An intravenous regional antibiosis using 10 Mega I.U . Sodium-Benzylpenicillin was carried out during surgery in 14 dairy cows affected with spontaneous occurring digital diseases . Blood serum and milk serum levels were determined over a period of 48 hours by means of a micro agar diffusion method using Sarcina lutea Stamm BGA Berlin as a test germ . Even before opening of the rubber tourniquet, penicillin traces were detectable in the blood serum of 6 cows . Maximal concentrations ranging from 0.43 mcg/ml to 8.63 mcg/ml were determined after 45 minutes to 4 hours . 24 hours after intravenous regional antibiosis no levels above the limit of detectability were determined . Significant lower maximal concentrations were found in claw amputation cases as compared with claw preserving surgical interventions . Milk serum levels showed delayed and lower maximal concentrations, ranging between 2.09 and 0.09 mcg/ml . In 5 animals no positive levels were detected . After 48 hours, penicillin levels were below the limit of detectability in the milk of all examined animals.

Voen Med Zh, 1994 Aug, (8), 31 - 4, 79
{Croupous pneumonia: current problems and means for their resolution}; Alekseev VG et al.; Croupous pneumonia makes up to 7-8% of all pneumonia cases in different regions of the country . 83 lethal outcomes have been studied . In 46 cases pneumonia was primary illness and the direct cause of death . In case a pneumonia is diagnosed an urgent hospitalization and penicillin treatment (maximum effect on pneumococcus is ensured with 1.8-2.4 million units per day) are necessary . For the prevention of acute cardiovascular insufficiency camphor is prescribed for 2-3 days . Mucolytic preparations and--after normalization of temperature--physiotherapeutic methods and therapeutic exercises are used for treatment . In 25-46.6% of lethal cases pneumonia is not diagnosed in their lifetime . Late hospitalization influencing illness's outcome takes place in 73% of cases.

Enzyme Microb Technol, 1994 Aug, 16(8), 715 - 8
Enzymatic production of cephalexin; Maladkar NK; Enzymatic production of cephalexin using immobilized penicillin G acylase was studied . The factors that affect the conversion of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) to cephalexin, such as pH; temperature; concentrations of 7-ADCA, D(-)-phenylglycine methyl ester (PGME), and immobilized penicillin G acylase (IMPGA); time; and molar ratios of 7-ADCA and PGME, were investigated . Under optimized conditions, 85% conversion of 7-ADCA to cephalexin was achieved . The IMPGA was used for 10 cycles.

Biochem Mol Biol Int, 1994 Aug, 34(1), 201 - 7
Catalytic activity of refolded penicillin acylase subunits in aqueous solution and aerosol ot reversed micelles in octane; Kabakov VE et al.; Refolded alpha and beta subunits of penicillin acylase were produced by gel-filtration under denaturing conditions followed by removal of urea through dialysis . Preparations of both renatured subunits hidrolysed specific substrate--phenylacetic acid p-nitroanilide in buffer and in the system of Aerosol OT reversed micelles, the alpha subunit being most catalytically active at Wo = 11.9, while the beta subunit--at Wo = 17.5 . There was a good correlation between the position of the found maxima, the theoretically calculated optimal hydration degrees as well as the earlier reported profile of enzymatic activity for native enzyme in reversed micelles.

J Bacteriol, 1994 Aug, 176(16), 4941 - 8
Molecular characterization of three loss-of-function mutations in the isopenicillin N-acyltransferase gene (penDE) of Penicillium chrysogenum; Fernandez FJ et al.; Five mutants of Penicillium chrysogenum blocked in penicillin biosynthesis (npe) which are deficient in isopenicillin N-acyltransferase were isolated previously . Three of these mutants, npe6, npe7, and npe8, have been characterized at the molecular level and compared with npe10, a deletion mutant . Transcripts of normal size (1.15 kb) of the penDE genes, which encode isopenicillin N-acyltransferase, and also of the pcbAB (11.5 kb) and pcbC (1.1 kb) genes were observed in all mutants except for the npe10 mutant . Immunoblotting studies using antibodies against isopenicillin N-acyltransferase showed that all mutants (except npe10) formed the 40-kDa (unprocessed) protein and the 29-kDa subunit of the isopenicillin N-acyltransferase . The 11-kDa subunit could not be observed in the immunoblots . The mutant penDE genes of strains npe6, npe7, and npe8 were cloned and sequenced . These three strains showed a mutation in the penDE genes which results in a single amino acid change in each modified isopenicillin N-acyltransferase . The mutation in npe6 resulted in a change of Gly-150 to Val, whereas the mutation in both npe7 and npe8 introduced a change of Glu-258 to Lys . Replacement of the Val-150 and Lys-258 mutations by constructing hybrid isopenicillin N-acyltransferase molecules led to the recovery of the isopenicillin N-acyltransferase activity . The mutations in npe6, npe7, and npe8 do not affect the ability of the 40-kDa isopenicillin N-acyltransferase to be processed into the component subunits.

Biochemistry, 1994 Jul 19, 33(28), 8417 - 27
X-ray crystallographic studies of a series of penicillin-derived asymmetric inhibitors of HIV-1 protease; Jhoti H et al.; In the development of a treatment for AIDS, the HIV-1 protease has been identified as a good target enzyme for inhibitor design . We previously reported a series of dimeric penicillin-derived C2-symmetric HIV-1 protease inhibitors {Humber, D., et al . (1993) J . Med . Chem . 36, 3120-3128} . In an attempt to reduce the size and optimize the binding of these C2-symmetric inhibitors, molecular modeling studies led to a novel series of monomeric penicillin-derived inhibitors of HIV-1 protease . The binding modes of these monomeric inhibitors have been characterized by X-ray crystallographic and NMR studies . Crystal structures of HIV-1 protease complexed to three inhibitors (GR123976, GR126045, and GR137615) from this series identify the molecular details of the interactions . The binding of GR123976 (IC50 = 2.3 microM) exhibits good hydrophobic contacts but few electrostatic interactions . A strategy of structure-based design and chemical synthesis led to the elaboration of GR123976 to optimize interactions with the protein . Crystallographic analysis of HIV-1 protease complexed to GR126045 and GR137615 identified these interactions with the catalytic aspartates and the protein binding pockets . The crystal structures of the three complexes confirm the presence of the major interactions modeled in order to optimize potency and reveal details of the molecular recognition by HIV-1 protease of this novel series of nonpeptidic inhibitors.

Neurosci Lett, 1994 Jul 18, 176(1), 71 - 4
Inhibitory mechanisms terminating paroxysmal depolarization shifts in hippocampal neurons of rats; Domann R et al.; The mechanisms responsible for the termination of paroxysmal depolarization shifts (PDS) were studied with intracellular recordings on CA1 neurons of rat hippocampal slices . Epileptiform activity was induced by application of penicillin, bicuculline or Mg-free artificial cerebrospinal fluid (ACSF) . PDS in penicillin-containing and Mg-free ACSF were markedly prolonged when GABAA-dependent IPSPs were blocked by bicuculline . PDS in bicuculline-containing ACSF were furthermore prolonged after block of potential dependent K+ conductances by TEA . TEA also exerted some effect on PDS induced by penicillin containing or Mg-free ACSF . Block of GABAB-dependent IPSPs or Ca(2+)-dependent K+ currents did not affect PDS duration in any of the three models . It is concluded that PDS termination is due to active inhibitory processes which comprise different components . If one of these components is blocked another inhibitory component governs PDS repolarization resulting in PDS with a slightly different duration but otherwise unchanged features.

Biochem J, 1994 Jul 15, 301 ( Pt 2), 485 - 94
Catalytic mechanism of active-site serine beta-lactamases: role of the conserved hydroxy group of the Lys-Thr(Ser)-Gly triad; Dubus A et al.; The role of the conserved hydroxy group of the Lys-Thr(Ser)-Gly {KT(S)G} triad has been studied for a class A and a class C beta-lactamase by site-directed mutagenesis . Surprisingly, the disappearance of this functional group had little impact on the penicillinase activity of both enzymes . The cephalosporinase activity was much more affected for the class A S235A (Ser235-->Ala) and the class C T316V (Thr315-->Val) mutants, but the class C T316A mutant was less impaired . Studies were extended to beta-lactams, where the carboxy group on C-3 of penicillins or C-4 of cephalosporins had been modified . The effects of the mutations were the same on these compounds as on the unmodified regular penicillins and cephalosporins . The results are compared with those obtained with a similar mutant (T299V) of the Streptomyces R61 DD-peptidase . With this enzyme the mutation also affected the interactions with penicillins and severely decreased the peptidase activity . The strict conservation of the hydroxy group on the second residue of the KT(S)G triad is thus much more easy to understand for the DD-peptidase and the penicillin-binding proteins than for beta-lactamases, especially those of class C.

Biochem J, 1994 Jul 15, 301 ( Pt 2), 477 - 83
The mechanism of action of DD-peptidases: the role of Threonine-299 and -301 in the Streptomyces R61 DD-peptidase; Wilkin JM et al.; The side chains of residues Thr299 and Thr301 in the Streptomyces R61 DD-peptidase have been modified by site-directed mutagenesis . These amino acids are part of a beta-strand which forms a wall of the active-site cavity . Thr299 corresponds to the second residue of the Lys-Thr(Ser)-Gly triad, highly conserved in active-site beta-lactamases and penicillin-binding proteins (PBPs) . Modification of Thr301 resulted only in minor alterations of the catalytic and penicillin-binding properties of the enzyme . No selective decrease of the rate of acylation was observed for any particular class of compounds . By contrast, the loss of the hydroxy group of the residue in position 299 yielded a seriously impaired enzyme . The rates of inactivation by penicillins were decreased 30-50-fold, whereas the reactions with cephalosporins were even more affected . The efficiency of hydrolysis against the peptide substrate was also seriously decreased . More surprisingly, the mutant was completely unable to catalyse transpeptidation reactions . The conservation of an hydroxylated residue in this position in PBPs is thus easily explained by these results.

Int J Syst Bacteriol, 1994 Jul, 44(3), 479 - 84
Mycoplasma auris sp . nov., Mycoplasma cottewii sp . nov., and Mycoplasma yeatsii sp . nov., new sterol-requiring mollicutes from the external ear canals of goats; DaMassa AJ et al.; Three mycoplasma strains, designated GIHT (T = type strain), UIAT, and VIST, were isolated from the external ear canals of goats and were shown to be serologically distinct from each other and from previously described Acholeplasma, Entomoplasma, Mesoplasma, and Mycoplasma species . Using light and transmission electron microscopy, we showed that the cells of these organisms were small, pleomorphic, coccoid, nonmotile, and nonhelical and that each cell was surrounded by a single cytoplasmic membrane . There was no evidence of a cell wall, and the organisms grew freely in media containing penicillin at concentrations of 1,000 U/ml or more and thallous acetate (final concentration, 1:4,000) and produced the "fried-egg" morphology typical of most mollicutes . Growth occurred both aerobically and anaerobically (as determined by the GasPak method) . The ability to catabolize glucose and mannose and the ability to hydrolyze arginine varied among the three strains . All three strains required sterol for growth, and none of the strains hydrolyzed urea . The guanine-plus-cytosine contents of the DNAs of strains UIAT, VIST, and GIHT were determined to be 26.9, 27.0, and 26.6 mol%, respectively . Our data indicate that the three strains represent new Mycoplasma species, for which we propose the names Mycoplasma auris, Mycoplasma cottewii, and Mycoplasma yeatsii . The type strain of M . auris is UIA (= ATCC 51348 = NCTC 11731), the type strain of M . cottewii is VIS (= ATCC 51347 = NCTC 11732), and the type strain of M . yeatsii is GIH (= ATCC 51346 = NCTC 11730).

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