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Biomedical subjects

A M Lerner

Publications and source records attributed to A M Lerner.

At least 19 recordsLinked to original sources
PubMed1979

Synergy between carbenicillin and an aminoglycoside (gentamicin or tobramycin) against Pseudomonas aeruginosa isolated from patients with endocarditis and sensitivity of isolates to normal human serum.

Isolates from the blood of 30 patients with endocarditis due to Pseudomonas aeruginosa were tested for synergy between carbenicillin and an aminoglycoside, either gentamicin or tobramycin, by in vitro checkerboard methods in modified (cation-supplemented) Mueller-Hinton broth. Twenty-five of the 30 isolates were affected synergistically. Whether given low (2.5--5 mg/kg) or high (8 mg/kg) doses of aminoglycoside along with 30 g of carbenicillin daily, all of the five patients infected with pseudomonads that were not synergistically affected were refractory to treatment with pseudomonads that were not synergistically affected were refractory to treatment with the carbenicillin-gentamicin combination, whereas the finding of synergy of carbenicillin with gentamicin (or tobramycin) did not assure a medical cure. Tests for synergy between carbenicillin and gentamicin yielded different results in Mueller-Hinton agar than in modified Mueller-Hinton broth. The majority (28) of 30 isolates of endocarditis-producing P. aeruginosa were resistant to the bactericidal effects of 50% pooled normal serum that had been freshly separated. One of the endocarditis-producing strains that was sensitive to 50% serum was resistant to 10% serum. However, sensitivity or resistance to freshly separated, pooled normal human serum did not predict the outcome of antibacterial therapy for pseudomonas endocarditis.

Aminoglycosides↗
PubMed1979

Modified polyriboinosinic-polyribocytidylic acid complex: sustained interferonemia and its physiological associates in humans.

Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.

Adolescent↗
PubMed1979

Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis.

Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis.

Animals↗
PubMed1978

Simultaneous serum and CSF antibodies in herpes simplex virus encephalitis.

Serial concomitant paired sera (S) and CSF were taken from eight patients with biopsy-proved herpes simplex virus encephalitis (HSVE). These specimen pairs were compared with 28 others from patients with various neurologic conditions. Before and after reduction with 2-mercaptoethanol, a ratio of S/CSF antibody titers of less than or equal to 20 with either the passive hemagglutinating (PHA) or immune adherence hemagglutinating (IAHA) antibody tests occurred in every patient with HSVE. Diagnostic S/CSF ratios were noted in three patients before biopsy of the brain and in four patients by the tenth day of neurologic disease. Among control subjects, a ratio of S/CSF titers greater than 20 was observed in all but four patients. Each of the latter patients had neurologic diagnoses easily distinguishable from HSVE. The PHA or IAHA S/CSF ratio offers a rapid, reliable method for the diagnosis of HSVE (P less than .001).

Adult↗
PubMed1978

Coxsackievirus B4 myocarditis in mice: valvular changes in virus-infected and control animals.

Suckling, weanling, and adult HaM/ICR and Swiss-Webster mice were inoculated intraperitoneally with the TC631 and Dowell strains of coxsackievirus B4. Vero cell-inoculated and uninoculated control mice were also studied under code. An intense, necrotizing myopericarditis was produced in suckling mice; it was less severe in weanlings. Myocarditis did not occur when coxsackievirus B4 was inoculated into adult mice. Progressive sclerosis and thickening of all valves in both strains of mice were observed with equal frequency in infected and control mice. There was no evidence that coxsackievirus B4 induced a specific valvular or endocardial lesion.

Animals↗
PubMed1978

Non-traumatic gram-negative bacillary meningitis in the Detroit Medical Center, 1964-1974; (with special mention of cases due to Escherichia coli).

Clinical and autopsy records of eight adults with non-traumatic gram-negative bacillary meningitis who were admitted to the hospitals of the Wayne State University--Detroit Medical Center during the years 1964 to 1974 were reviewed. There were five community-acquired cases, and five patients died. Escherichia coli was the causative enteric bacillus in six cases. Community-acquired infections were due to Esch. coli in four of the patients. Each of the patients with a community-acquired infection was a chronic alcoholic. Esch. coli bronchopneumonias, urinary infections, and bacteremias seeding the meninges were usual. Shunting contaminated portal venous blood through the liver in patients with Laennec's cirrhosis, or bypassing the liver with similar infected blood from a genitourinary source by way of Batson's perivertebral plexus draining into the cerebral dural sinuses may be important in the pathogenesis of these infrequent cases of nontraumatic gram-negative bacillary meningitis. Spontaneous gram-negative bacteremias, peritonitis, bronchopneumonias, and now "meningitis" may be a constellation of special complications of the alcoholic. Mortality among 25 patients with Esch. coli meningitis reported from 1922 to 1974 is approximately 50%, and has not changed appreciably during the antibiotic era. Mortality, however, is significantly higher in nosocomially acquired cases. Early and more recent cases have had bloody, xanthochromic pleocytoses indicative of leptomeningeal arterial and venous vasculitis, and far advanced disease. Since causative/enteric bacilli have been susceptible to antimicrobial agents employed, another mode of antibacterial administration, perhaps utilizing parenteral plus intraventricular dosing, particularly for patients acquiring their infections in the hospital, may be required.

Adult↗
PubMed1978

Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination.

The minimum inhibitory concentration (MIC) of adenine arabinoside (ara-A) in rabbit kidney microtiter tissue cultures (RK-13) to a prototype strain of herpes simplex virus, type 1 (E115) based upon inhibition of cytopathic effects is 1.5 mug/ml. In this system, the MIC of arabinosylhypoxanthine (ara-Hx), the major in vivo metabolic derivative of ara-A, is 75 mug/ml. Inhibition of cytopathic effects of herpes simplex virus, type 1 (HSV-1) in microtiter wells of RK-13 cells varies directly with the concentrations of ara-A or ara-Hx, and inversely with residual HSV-1. The MIC of ara-A for HSV-1 in RK-13 cells is 5-20 times lower than similar measures with vero renal, mouse embryo, or human foreskin cultures. With RK-13 tissue cultures in microtiter plates, an assay for "ara-A equivalents" in human body fluids was developed which compares in sensitivity with high pressure liquid chromatography and has the advantage of simultaneously measuring combined antiherpesvirus effects of ara-A and its major metabolic derivative, ara-Hx. In vitro checkerboard studies in RK-13 cells confirmed that ara-A and ara-Hx in combination had antiviral effects which are synergistic. The total of the fractional MIC of ara-A plus ara-Hx in combination also varies inversely with residual HSV-1 in microtiter wells. Because virus adsorption is complete at 2 h before specimens to be tested are added in this assay, and because human interferon is not measured in rabbit cells, the antiviral assay is not affected by the presence of type-specific antiherpesvirus antibody or human interferon.Antiviral activity (AVA) was assayed as ara-A equivalents in sera and urines from 10 patients with serious herpesvirus infections who received 2.5-20 mg/kg daily of ara-A by intramuscular or intravenous routes. When a dosage schedule of 10 mg/kg per day or more was used, sustained concentrations of AVA that ranged from 0.8 to 14.4 mug/ml were found. When an inhibitor of adenosine deaminase (covidarabine) was not added to the specimens, mean serum concentrations were congruent with3.0 mug/ml (10 mg/kg per day, i.v.), and 4.1 mug/ml (20 mg/kg per day). However, in a single patient given 20 mg/kg of ara-A daily with covidarabine immediately added to the sera, the mean concentration of AVA was 12.9 mug/ml. Urines contained even higher AVA. Assays of 19 sera were performed both by microbiologic assay for AVA and by high pressure liquid chromatography for ara-A and ara-Hx. AVA was greater by microbiologic assay, and was greater than that which could be accounted for by stoichiometric chromatographic measures of ara-A and ara-Hx. These results with sera of treated patients are consistent both with the in vitro synergy of ara-A and ara-Hx found by checkerboard titrations, and with the beneficial responses to ara-A of patients with herpesvirus infections reported here and elsewhere.

Adult↗
PubMed1978

Some previously unrecognized features of herpes simplex virus encephalitis.

The courses of 15 brain biopsy-proven cases of herpes simplex virus encephalitis (HSVE) were followed for 6 to 67 months. Convulsive disorders were often temporary, but paralysis was permanent. Patients usually entered the hospital free of paralysis or coma, in a potentially reversible febrile confusional state. Later, paralysis and coma fixed subsequent courses. Mortality was 53.3 percent but, at follow-up, 93.3 percent (14 patients) were dead or living a vegetative existence at home or in institutions. If a definitive diagnosis of HSVE could be made at the time of hospital admission, the prognosis might be remarkably changed.

Adolescent↗
PubMed1977

Differentiation of several isolates of Peptococcus magnus by counterimmunoelectrophoresis.

Uniform sonicated suspensions of three clinical isolates of Peptococcus magnus that were morphologically, chromatographically, and biochemically identical were used to produce hyperimmune antisera in rabbits. Similar hyperimmune serum was prepared to a single strain of Peptostreptococcus anaerobius. When these antisera and antigens were tested by counterimmunoelectrophoresis, the three isolates of Peptococcus magnus were immunologically distinct. None of the antisera to Peptococcus magnus formed precipitin lines with Peptostreptococcus anaerobius.

Animals↗
PubMed1977

Inhibitory and lethal concentrations of 9-beta-D-arabinofuranosyladenine and its hypoxanthine-derivative versus herpes simplex virus, type 1.

Minimum inhibitory concentrations of 9-beta-D-arabinofuranosyladenine (ara-A, adenine arabinoside, vidarabine) and a purified preparation of 9-beta-D-arabinofuranosylhypoxanthine (arabinoslhypoxanthine, ara-Hx) at end points of 50% MIC50) and 100% (MIC100) reduction to challenges of approximately 50 p.f.u. of herpes simplex virus, type 1 (HSV-1) were determined in vero renal tissue cultures. Adenosine deaminase is universally present in tissue cultures and serum. These same tests were repeated in the presence of a potent inhibitor of adenosine deaminase, R-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo-4,5-d)-(1,3)-diazepin-8-ol (co-vidarabine, co-ara-A). Addition of co-ara-A to assays of MIC50 or MIC100 for ara-A ensures standard reproducible results which can be compared in different laboratories. After incubations of HSV-1 in infected cultures for 96 hours, 35 degrees C., with concentrations of ara-A or ara-Hx at the MIC100 and over, cells were scraped and sonicated. Supernates were then reinoculated into vero flasks free of antiviral agents to determine minimum lethal concentrations (MLC's). Standard values (microng/ml.) for ara-A with co-ara-A are 11.3 (MIC50), 17.0 (MIC100), and 34.0 (MLC) but are 68.1 (MIC50), 170.4 (MIC100) and 375 (MLC) for ara-Hx. These data confirm that as a virustatic agent (MIC100) ara-A is 10 times more active than ara-Hx. Ara-A and ara-Hx have virucidal potentials which require approximately two times the respective MIC100.

Arabinonucleosides↗
PubMed1976

Microbiologic assays and neurological toxicity during use of adenine arabinoside in humans.

Patients with herpesvirus infections were given intravenous injections of 10-20 mg of adenine arabinoside (ara-A)/kg per day. When given the higher dosage, some patients with chronic hematologic conditions showed mild to moderate additional depressions in the level of hemoglobin. The number of neutrophils and platelets did not decrease, even when numbers were low at the onset of treatment with ara-A. Two patients with Hodgkin's disease who received 20 mg of ara-A/kg per day developed a transient motor aphasia resembling akinetic mutism. With the regimens of ara-A used and challenge inocula of approximately 50 plaque-forming units of virus, the minimal inhibitory concentrations of ara-A and hypoxanthine arabinoside for herpesviruses are usually not achieved in serum but may be attained in body fluids (urine and vesicular fluid). Antiviral activity in vesicular fluids is likely to involve a combination of ara-A, hypoxanthine arabinoside, and interferon.

Akinetic Mutism↗