Biomedical subjects
Publications and source records attributed to H Miller.
A case is reported of an infant who experienced seizures while being treated with a topical lidocaine 2% solution (Xylocaine 2% Viscous) for teething. The pharmacology of lidocaine is reviewed to alert physicians to the potential dangers of topical mucosal application of these preparations.
10 patients with serious infections caused by Staphylococcus epidermidis (8 cases of endocarditis in non-prosthetic valves, 1 was complicated by osteomyelitis, 1 case of osteomyelitis, and 1 case of septicemia) are described. Clinical and microbiologic features were evaluated including antibiotic sensitivity and synergy studies, phage typing and biotyping. Endocarditis tended to affect the elderly population and the clinical manifestations were quite similar to those caused by Streptococcus viridans. Both patients with osteomyelitis had involvement of the cervical spine with excellent response to antibiotic therapy. The only patient with septicemia acquired via hyperalimentation had delayed clearance of the bacteremia but ultimately responded to intravenous antibiotics. Rifampicin was the most effective of all antibiotics tested. All isolates were sensitive to penicillinase-resistant penicillins and cephalosporins and over half were sensitive to penicillin. Full synergistic activity was demonstrated with cephalothin and nafcillin in combination with rifampicin, and rifampicin-vancomycin was partially synergistic against the majority of the strains. Five of 8 available isolates were non-phage typeable and no definite pattern was established for various types of infections. Four of the 8 isolates were classified as biotype SIIa, 2 biotype SIIc and 2 biotype SVh.
Human erythrocytes parasitized with Plasmodium falciparum, obtained from in vitro continuous cultures and stored at -185 degrees C and at -70 degrees C for several months, were successfully recovered. Ten per cent glycerol or 10% dimethyl sulphoxide in growth medium RPMI 1640 were used and found equally effective as cryopreservatives. This simplified method does not require centrifugation or special media before storage or after recovery of the parasites. The viability of the parasites is monitored in vitro by initiating new continuous cultures.
To study the natural course of catheter-induced endocarditis secondarily infected with Staphylococcus epidermidis, 29 rabbits had catheters introduced surgically through the carotid artery to the aortic valve. Forty-eight hours later the catheters were removed from five rabbits. The rabbits were inoculated intravenously with 10(8) colony-forming units of S epidermidis. Autopsies done at various intervals showed all rabbits with indwelling catheters had noticeable aortic valve vegetations with positive cultures for S epidermidis. In the group with catheters removed after 48 hours, less severe valvular lesions were noted. Metastatic seeding to kidneys, spleen, and liver were noted in both groups. Because of low cure rate in the treatment of S epidermidis endocarditis, this rabbit model could be used to study antibiotic regimens for valvular endocarditis.
An ultrastructural study of asteroid bodies in a vitreous aspirate from a patient suffering visual loss as a result of asteroid hyalosis is presented. Under appropriate conditions of fixation and high resolution transmission electron microscopy, a lamellar arrangement with a periodicity of 4.6 nm was observed. This lamellar arrangement is typical of liquid crystalline phases of lipids in water. X-ray micro-analysis confirmed the presence of calcium and phosphorus in the asteroid bodies. We propose that the asteroid bodies are not true crystals but rather liquid crystals of phospholipids in the vitreous humor.
Subjects identified on the basis of sex, handedness, and handwriting posture performed a letter-naming task. Single letters were shown briefly in the left or right visual field and the subject was required to name the letter as quickly as possible. Both left- and right-handers had shorter response latencies when the stimulus was presented in the left visual field. Response latency decreased across trials, however, the decrement was largest to right visual field stimuli. In addition, males produced significantly faster reaction than did females.
An improved high-pressure liquid chromatography system was used to analyze the amount of benzo[a]pyrene metabolites formed in reconstituted microsomal mixed-function oxidase systems containing different cytochromes P-450. We separated twelve identified and seven unknown metabolites of BP which included three diols: the 9,10-, 4,5-and 7,8-dihydrodiols; four phenols, 9-,7-, 1-, and 3-hydroxybenzo[a]pyrene (OH-BP); and three quinones: the 1,6-. 3,6-, and 6,12-quinones. Two additional peaks co-migrated with synthetic 4-OH-BP and 5-OH-BP, respectively. The former, designated fraction 1, was shown by u.v. spectra to contain primarily the 4,5-epoxide with small amounts of 4-OH-BP. The total metabolism of BP was found to be approximately 20-fold greater with the cytochrome P-450 from the 3-methylcholanthrene (P-450 3-MC) and beta-naphthoflavone (P-450 BNF) treated rats than with the phenobarbital preinduced cytochrome P-450 (P-450 BP). 3-OH-BP ad 9-OH-BP were the major phenolic products for both P-450 3-MC and P-450 BNF whereas the 3-OH-BP and 1-OH-BP were the major phenolic products for P-450 BP. The ratio of total phenols to diols was found to be 3.34, 4.85 and 0.70 for P-450 3-MC, P-450 BNF and P-450 PB. The major dihydrodiol generated by P-450 3-MC and P-450 BNF was 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, whereas the 9,10-diol was the major diol from P-450 PB. The amount of 1,6- and 3,6-quinones produced was greater than the 6,12-quinone with the P-450 3-MC and P-450 BNF but all three quinones were produced in low and equal amounts by the P-450 PB. In respect to the percent metabolites formed at a given region of the BP, P-450 3-MC and P-450 BNF preferred oxidation at the 1, 3 positions, 6 position and the 7, 8 positions, whereas the P-450 PB preferred oxidation at the 4, 5 position. This study demonstrates the unique positional specificity of different forms of cytochrome P-450 which may regulate the balance between activation and detoxification pathways of polycyclic aromatic hydrocarbon metabolism.
Antibiotic susceptibility and synergy were studied in 12 clinical isolates of Listeria monocytogenes from patients with meningitis and septicemia. Rifampin and trimethoprim-sulfamethoxazole (TMP-SMX) were the most potent single drugs tested. Approximately 80% of the strains demonstrated full synergistic bactericidal activity with rifampin in combination with penicillin or ampicillin. Clinical experience dictates that ampicillin or penicillin should remain the antibiotic of choice in the treatment of severe infections, such as meningitis caused by L. monocytogenes. Where the use of penicillin is contraindicated (e.g., allergy or failure to respond), use of TMP-SMX might be considered. Further in vitro and vivo studies are needed before therapy with rifampin or TMP-SMX in combination with penicillin or ampicillin can be recommended.
Tiapamil has been extensively investigated for treatment of cardiac arrhythmias. Concern persists, however, that, as a calcium antagonist, it may seriously depress myocardial function. To investigate this possibility, 20 patients were given tiapamil intravenously and studied by radionuclide ventriculography. Tiapamil markedly lowered arterial pressure. Left ventricular ejection fraction increased from 54 +/- 3.3 to 57 +/- 3.3%. No significant change in heart rate was noted. Tiapamil did not increase the extent of left ventricular asynergy. The potent vasodilator properties of tiapamil compensate for any intrinsic decrease in left ventricular contractibility, and therefore overall cardiac function is not worsened by the drug in patients with normal or moderately reduced resting ventricular ejection fractions.
Monoclonal antibodies were prepared from hybridoma clones isolated by the fusion of myeloma cells and spleen cells derived from mice immunized with either purified rabbit liver microsomal cytochrome P-450LM2 or cytochrome P-450LM4. Seven hybridoma clones produced three kinds of monoclonal antibodies to P-450LM2. The first class bound, precipitated, and inhibited the enzyme activity of P-450LM2 for both benzo[a]pyrene hydroxylation and 7-ethoxycoumarin deethylation. The other two classes either bound and precipitated or only bound the enzyme. These monoclonal antibodies to P-450LM2 showed a precipitin reaction and inhibition of enzyme activity that was specific for cytochrome P-450LM2. Thus, they did not react with or inhibit the enzyme activity of the other isozyme cytochrome P-450LM4, Fraction 1 or Fraction 7. All of the monoclonal antibodies formed against P-450LM2 were mouse immunoglobulin (Ig) subclass IgG1. The most effective monoclonal antibody strongly inhibited the formation of oxygenated metabolites of benzo[a]pyrene at various positions as well as the deethylation of 7-ethoxycoumarin. Four hybridomas were isolated which produced monoclonal antibodies to P-450LM4. One of the four was of the IgM class and three were of the IgG1 type. The four monoclonal antibodies bound to P-450LM4 but did not precipitate the enzyme, and did not bind to P-450LM2. The monoclonal antibody P-450LM4 complexes interacted with protein A, and the enzyme activity for benzo[a]pyrene hydroxylation could be removed by centrifugation. The high specificity and monoclonality of these antibodies suggest their potential usefulness for studying the genetics, regulation, and roles of the different isozymes of P-450LM in drug and carcinogen metabolism.
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A satisfactory, simple test for screening and monitoring of patients with prostatic cancer is still being sought. We suggest the use of a nonspecific test in combination with other tests. The ratio of two serum proteins (alpha 1 acid glycoprotein [AGP] and prealbumin [PAB]), may be useful markers for a cancer serum index (CSI). By separating serum components by gradient polyacrylamide gel electrophoresis, staining and quantitating these proteins by scanning densitometry, and dividing the area of AGP by that of PAB, indices can be obtained. In a test of sera from 450 patients with prostatic cancer, other urologic problems, and normal controls, CSIs of 360 sera presently decoded were found to be: (Formula: see text). The CSI should prove highly valuable when used in combination with selected prostatic cancer tests.
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Aryl hydrocarbon hydroxylase (AHH) activity was detected in a variety of guinea pig lymphoid tissues and was increased by intradermal or ip administration of 3-methylcholanthrene AHH levels were generally greater in spleen than in lymph node, bone marrow, or thymus. Similar AHH activities were observed in lymphoid tissues from Sewall-Wright inbred strain 2 and strain 13 guinea pigs. Greater AHH activities were associated with peritoneal and alveolar macrophages than with lymph nodes lymphocytes in the absence of mitogens.
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Analysis of amino acid and nucleotide sequences of kappa immunoglobulin chains and their genes has led to the hypothesis that the exact site of V-J joining in these genes varies and that this variation is partially responsible for generating amino acid diversity at the recombination site. To assess this hypothesis we have cloned and determined the sequence of one of the two V-J recombinant genes carried by the plasmacytoma MOPC173 and the V region germline precursor of this gene. We find that this V region has been joined to a J segment at a crossover point that indeed differs from the one previously described. This recombination has occurred in such a way as to produce an out of phase, missense reading frame and, hence, a cryptic light chain gene. This result directly supports the cross-over-point variation hypothesis but also indicates that the flexibility of this reaction is accompanied by a cost to the organism in terms of the generation of missense genes.