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Biomedical subjects

T W Williams

Publications and source records attributed to T W Williams.

At least 19 recordsLinked to original sources

Comparison of polymerase chain reaction and chlamydiazyme for the detection of Chlamydia trachomatis in clinical specimens.

An attempt was made to improve laboratory diagnosis of Chlamydia trachomatis and to validate the Abbott Chlamydiazyme confirmatory test used at present by comparing the polymerase chain reaction (PCR) procedure and the Abbott enzyme immunoassay. A total of 275 routine clinical specimens representing a range of positive and negative findings by Chlamydiazyme were retested by PCR. The procedures demonstrated 99% concordance for specimens with optical density (OD) readings above the Chlamydiazyme cut-off of 0.1, but PCR was confirmed to be significantly more sensitive (p less than 0.025) for specimens with OD values between 0.05 and 0.09. Specimens in this range should be retested routinely by PCR.

Chlamydia Infections

Successful medical management of a patient with multiple hepatic abscesses due to Edwardsiella tarda.

Isolation of Edwardsiella tarda in humans has been associated with an asymptomatic carrier state as well as mild, self-limited diarrheal illness. Extraintestinal manifestations have included soft-tissue infections, meningitis, osteomyelitis, cholangitis, and sepsis. Only three cases of patients who had documented hepatic abscess due to E. tarda have been reported in the English-language literature; two patients died, and the third required a laparotomy and drainage. We report what is, to our knowledge, the first autochthonous case of hepatic abscess due to E. tarda in the United States and the first case that was successfully managed with antibiotic therapy alone.

Adult

Considerations in dosage selection for third generation cephalosporins.

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

Acute Kidney Injury

Appearance of ductular hepatocytes in rat liver after bile duct ligation and subsequent zone 3 necrosis by carbon tetrachloride.

Intrahepatic biliary cell plasticity was investigated in a rat model that combined prior bile ductular cell hyperplasia after bile duct ligation with subsequent CCl4-induced hepatonecrosis. Morphometric analysis of histologic liver sections from rats at 4 to 6 weeks after bile duct ligation and 3 to 5 days after CCl4 demonstrated the total section area to be occupied by near-equal amounts of hyperplastic bile ductular tissue area and hepatonecrotic area. Of particular significance was the unique presence, albeit infrequent, of newly appearing hepatic cell cholangioles composed of both biliary epithelial cells and one or more 'ductular hepatocytes' exclusively within the hyperplastic bile ductular tissue area of liver sections from the bile-duct-ligated/CCl4-treated rats, but not observed in control liver sections. This finding is compatible with the possibility of a 'transdifferentiation' of some hyperplastic biliary epithelial cells into 'ductular hepatocytes' in response to an extreme hepatic injury.

Animals

Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy.

The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol-treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization.

Antibodies, Neoplasm

Anaerobic bacterial meningitis.

Anaerobic meningitis occurred in four patients in whom anaerobic bacteria had not been suspected as a possible cause. The predisposing conditions were typical of those seen in patients previously reported to have this infection and included chronic otitis media with mastoiditis, chronic sinusitis, recent craniotomy and abdominal trauma. Two of the patients had undergone immunosuppression (immunosuppressed patients); a compromised immune system may facilitate the development of anaerobic meningitis in patients with the appropritate underlying conditions. Head and neck neoplasms, head trauma, suppurative pharyngitis and laminectomy wounds are additional situations in which anaerobic meningitis occurs. Anaerobic bacterial meningitis probably occurs more often than is recognized. The cerebrospinal fluid should be transported and cultured anaerobically when meningitis develops in a patient with a predisposing condition.

Abdominal Injuries

Synergy of vancomycin plus cefazolin or cephalothin against methicillin-resistance Staphylococcus epidermidis.

The in vitro activity of cephalothin, cefazolin, and vancomycin against 25 isolates of methicillin-resistant Staphylococcus epidermidis was determined by means of a broth dilution technique with two sizes of inoculum. The size of the inoculum had a marked effect on the minimal inhibitory concentrations and the minimal bactericidal concentrations of all three antibiotics. With a small inoculum, 100% of the isolates were inhibited by 3.12 micrograms of vancomycin/ml, 76% by 12.5 micrograms of cephalothin/ml, and 64% by 12.5 micrograms of cefazolin/ml. With a large inoculum 100% of the isolates were inhibited by 200 micrograms of vancomycin/ml, 40% by 12.5 micrograms of cephalothin/ml, and 12% by 12.5 micrograms of cefazolin/ml. As determined by a tube dilution checkerboard technique for both sizes of inoculum, the combination of vancomycin plus cephalothin was synergistic against methicillin-resistant S. epidermidis in 45 of 50 cases, and the combination of vancomycin plus cefazolin was synergistic in 39 or 50 cases. These data from in vitro studies suggest that these antibiotic combinations should be evaluated clinically in patients with severe infections caused by methicillin-resistant S. epidermidis.

Cefazolin

Susceptibility and synergy studies of methicillin-resistant Staphylococcus epidermidis.

Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at </=3.12 mug/ml, whereas clindamycin inhibited only 46 strains at </=12.5 mug/ml. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of >/=3.12 mug/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at </=25 mug/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (>/=10(2) kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 mug/ml) plus cefamandole (6.25 mug/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 mug/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 mug/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 mug of rifampin per ml developed in three of five methicillin-resistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.

Anti-Bacterial Agents

Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice.

Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.

Animals

Allergic bronchopulmonary aspergillosis-like syndrome consequent to aspergilloma.

Two patients who represent the first well-documented cases of an allergic bronchopulmonary aspergillosis-like syndrome developing consequent to an aspergilloma are reported. These patients experienced both subjective and objective evidence of improvement after the initiation of corticosteroid therapy. Literature relevant to the combined occurrence of aspergilloma and allergic bronchopulmonary aspergillosis and their immunology is reviewed.

Adult

Agranulocytosis during therapy with orally administered cloxacillin.

Agranulocytosis developed in a patient with staphylococcal osteomyelitis after 35 days of treatment with orally administered cloxacillin. The patient had fever, prostration, pharyngitis, and profound leukopenia, which subsequently abated upon withdrawal of the drug. Cloxacillin should be included in the growing list of drugs capable of producing leukopenia and agranulocytosis.

Administration, Oral

Methicillin-resistant Staphylococcus epidermidis.

Staphylococcus epidermidis is frequently associated with infection of prosthetic heart valves, prosthetic orthopedic devices, and neurosurgical shunts. Penicillinase-resistant semisynthetic penicillins, such as methicillin, have been the therapeutic and prophylactic agents of choice for S epidermidis infection. However, more S epidermidis isolates are now resistant to methicillin and other penicillins. In our laboratory 41% of S epidermidis isolates were resistant to methici-lin. All of the methicillin-susceptible isolates and 82% of the methicillin-resistant isoates were susceptible to cephalothin. Cephalothin should replace methicillin as the prophylactic and therapeutic agent of choice in institutions with a high percentage of methicillin-resistant S epidermidis.

Cephalothin

Prosthetic valve endocarditis.

PVE is increasingly frequent and often lethal. The classic features of infective endocarditis may be absent early in the course of the illess. Therefore, patients with prosthetic heart valves and fever must be considered candidates for this infection until another cause for the fever can be established. Five to six blood cultures will document the persistent bacteremia of PVE in most cases. Treatment consists of parenteral penicillins for sensitive organisms plus valvular re-replacement for intractable heart failure mechanical malfunction of the valve, persistent sepsis, or multiple major emboli. In spite of aggressive therapy, the mortality remains high. Therefore, appropriate prophylaxis is warranted in patients with prosthetic valves who must undergo procedures that might lead to bacteremia.

Anti-Bacterial Agents

Gastroenteritis in children: a two-year review in Manitoba. I. Etiology.

During two years, 1,217 children hospitalized with gastroenteritis at the Children's Centre in Winnipeg, Manitoba, Canada were studied. Bacterial pathogens were present in 25% of these children: enteropathogenic Escherichia coli in 120, Shigella in 139, Salmonella in 24, and multiple pathogens in 18. Rotavirus was detected in 54 (11%) of 472 patients examined. Rotavirus and enteropathogenic E. coli were the most common pathogens in infants, and Shigella was the most common in older children. Bacterial diarrhea occurred more commonly in summer, whereas rotavirus infection occurred more commonly in winter. Among 276 children screened, enterotoxigenic E. coli was found in three, and Aeromonas shigelloides that produced a similar toxin in two others. Enteroinvasive E. coli was not detected in 70 children. Organisms producing toxins "cytotoxic" to HeLa cells were isolated from three of 90 children. Screening for enterotoxigenic or enteroinvasive organisms was not productive of a significant number of pathogens, and, although screening for rotavirus did improve the number of etiologic diagnoses, the etiology of the majority of cases of diarrhea remained unknown.

Age Factors

Resistance to gentamicin: a growing concern.

Gentaminic was introduced in 1969 as a broad-spectrum aminoglycoside effective in vitro against a majority of aerobic gram-negative bacilli. In recent years gentamicin-resistant clinical isolates have become more prevalent. In our laboratory in 1975, 32% of Pseudomonas sp and 44% of indole-negative Proteus sp isolates were resistant to gentamicin. Resistance to tobramycin is also increasing; 24% of Escherichia coli and 28% of indole-negative Proteus sp isolates were found to be tobramycin-resistant. In addition, isolation of previously uncommon gentamicin-resistant species, ie, Proteus rettgeri and other indole-positive Proteus sp, from clinical specimens has increased dramatically in the past five years. This increase in gentamicin and tobramycin-resistant gram-negative bacilli serves as a constant stimulus for the development of new antimicrobial agents.

Drug Resistance, Microbial

In vitro lysis of target cells by rat polymorphonuclear leukocytes isolated from acute pyelonephritic exudates.

Polymorphonuclear (PMN) leukocytes from acute pyelonephritic exudates of rats were examined for cytoxicity against various target cells. Pyelonephritic PMN leukocytes caused lysis in vitro of syngeneic renal epithelial cells in 24 to 48 hr. They also caused lysis of allogeneic and xenogeneic target cells. The susceptibility to PMN-induced cytolysis was different among various target cell lines. Cell lysis proceeded at low ratios of effector to target cells and was not dependent on the addition of antibody or lectins. PMN isolated from peritoneal exudates (starch or endotoxin induced) were also cytoxic for the target cells. Cell-free supernatants from pyelonephritic PMN-target cell mixtures, or pyelonephritic PMN leukocytes cultured alone contained cytolytic substances which were nondialyzable and heat stable Finally, the urine of pyelonephritic rats was cytotoxic. These results suggest that PMN leukocytes and their cytotoxic mediators are directly involved in the pathogenesis of renal injury in pyelonephritis.

Animals