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Biomedical subjects

D Hardy

Publications and source records attributed to D Hardy.

At least 55 records · Page 3Linked to original sources
PubMed1994

Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team.

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

Interpretive criteria and quality control for antimicrobial susceptibility tests of levofloxacin.

To confirm preliminary interpretive breakpoints for prototype 5 micrograms levofloxacin disks, 490 strains were tested in vitro using commercially manufactured disks. For in vitro susceptibility testing, 5 micrograms levofloxacin disks can be used with interpretive criteria of < or = 12 mm for resistant (MIC > or = 8.0 micrograms/ml) and > or = 16 mm for susceptible (MIC < or = 2.0 micrograms/ml). Proposed quality control limits for tests of levofloxacin are as follows: Escherichia coli ATCC 25922, zones 29-37 mm or MIC 0.008-0.03 microgram/ml; Pseudomonas aeruginosa ATCC 27853, zones 19-26 mm or MIC 0.5-2.0 micrograms/ml; Staphylococcus aureus ATCC 25923, zones 24-31 mm; Staphylococcus aureus ATCC 29213, MIC 0.06-0.25 microgram/ml and Enterococcus faecalis ATCC 29212, MIC 0.25-2.0 micrograms/ml.

Bacteriological Techniques↗
PubMed1994

Use of refractometry to identify opioid-containing solutions.

The purpose of this laboratory study was to assess the value of refractometry in identifying the contents of a variety of opioid-containing solutions. A hand-held refractometer was used to document the refraction produced by the undiluted contents of alfentanil, fentanyl, morphine, sufentanil ampoules and by solutions of Ringer's lactate, 0.9% saline, 3.3% dextrose in 0.3% saline, and distilled water. Each opioid was then serially diluted in serial 1:2, 1:4, and 1:8 dilutions in each of these solutions and the refractions of each determined. Based on this information, blinded identification of various diluted opioid solutions was attempted. Refractometer values for undiluted fentanyl and sufentanil were identical with those for distilled water. Those for undiluted alfentanil and morphine were almost identical with each other and with 1:2 and 1:4 dilutions of either drug in Ringer's lactate or 0.9% saline. We conclude that refractometry is an unreliable screening method to detect tampering with opioid solutions.

Alfentanil↗
PubMed1993

Relative efficacy of tazobactam, sulbactam and clavulanic acid in enhancing the potency of ampicillin against clinical isolates of Enterobacteriaceae.

Three beta-lactamase inhibitors were combined with ampicillin in a fixed 2:1 ratio. The activity of ampicillin was enhanced by tazobactam and by clavulanic acid, and to a lesser extent by sulbactam when tested against fresh clinical isolates of Enterobacteriaceae. At a concentration of 8 micrograms/ml, ampicillin alone inhibited 49.6% of 2,434 consecutive isolates of enteric bacilli compared to 81% inhibited by ampicillin combined with tazobactam or clavulanic acid and 69.3% inhibited by the sulbactam/ampicillin combination. A four-fold or greater reduction in ampicillin MICs was observed in comparable numbers of isolates with all three combinations, but the most marked effects were seen with strains that were highly resistant to ampicillin.

Ampicillin↗
PubMed1993

Ampicillin-sulbactam susceptibility testing criteria.

In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of the Enterobacteriaceae against ampicillin-sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC < or = 16/8.0 micrograms/ml or < or = 8.0/8.0 micrograms/ml for the susceptible category. Disks containing 10 micrograms of ampicillin and 10 micrograms of sulbactam are still to be preferred with interpretive criteria of > or = 15 mm for susceptible and < or = 11 mm for resistant (MIC > or = 64/32 micrograms/ml or > or = 32/32 micrograms/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased.

Ampicillin↗
PubMed1993

A dose-ranging study of daily maintenance intravenous foscarnet therapy for cytomegalovirus retinitis in AIDS.

Thirty-two patients with AIDS and previously untreated cytomegalovirus retinitis completed an induction course of foscarnet, 60 mg/kg every 8 h for 14 days, had retinitis stabilize, and were then randomly assigned to receive foscarnet maintenance as either a 90- or 120-mg/kg/day infusion administered over 2 h. Median survival was 157 and 336 days for the 90- and 120-mg/kg/day groups, respectively (P < .001). In an independent, masked analysis of retinal photographs, median time to progression of retinitis was 31 versus 95 days (P = .13). Daily intravenous foscarnet at a dose of 120 mg/kg (adjusted for renal function) resulted in significantly longer survival and tended to increase time to retinitis progression compared to the standard 90-mg/kg/day maintenance dose. Although a substantial increase in the risk of serious toxicity at the 120-mg/kg/day dose was not observed, the small sample size in this trial limited the power to detect differences that might be clinically important.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Histological analysis of the bone/prosthesis interface in man after implantation of a hip prosthesis coated with plasma-sprayed hydroxyapatite].

Thin coatings of calcium phosphate hydroxyapatite on metal alloys provide to these materials biological properties of calcium phosphates. We have analysed, using histological techniques or newly developed scanning electronic microscopy techniques, hip prostheses implanted into humans for periods from a few days up to twenty six months. The results of these analyses confirm the good osteointegration of these prostheses observed during clinical studies. Moreover, an active remodeling of the bone in contact with the ceramic-coating was observed. The coating was also concerned by the remodeling process and evolved once implanted.

Bone Matrix↗
PubMed1992

Insertional mutagenesis of hydrophilic domains in the lactose permease of Escherichia coli.

The lactose permease of Escherichia coli is a membrane transport protein postulated to contain a hydrophilic N terminus (hydrophilic domain 1), 12 hydrophobic transmembrane alpha-helices that traverse the membrane in zigzag fashion connected by hydrophilic domains, and a hydrophilic C terminus (hydrophilic domain 13). To test whether the hydrophilic domains are important for function, each domain was independently disrupted by insertion of two or six contiguous histidine residues, and the mutants were characterized with respect to initial rate of lactose transport and steady-state level of accumulation. Remarkably, histidine insertions into 10 out of 13 hydrophilic domains result in molecules that catalyze lactose accumulation effectively, although the initial rate of transport is compromised in certain cases. In contrast, insertions into hydrophilic domain 3, 9, or 10 cause a marked decrease in transport activity. As judged by immunoblots and [35S]methionine pulse-chase experiments, diminished activity is not due to decreased expression of the mutated permeases, defective insertion into the membrane, or increased rates of proteolysis after insertion. The results (i) suggest that most of the hydrophilic domains in the permease do not play an essential role in the transport mechanism and (ii) focus on the region of the permease containing putative helices IX and X as being particularly important for activity.

Amino Acid Sequence↗
PubMed1992

Evidence that the final turn of the last transmembrane helix in the lactose permease is required for folding.

Although truncation of the hydrophilic C-terminal tail of the lactose (lac) permease of Escherichia coli (residues 401-417) has no significant effect on membrane insertion, stability, or transport activity, sequential substitution of stop codons for amino acid codons 398-401 leads to a progressive increase in transport activity and in the lifetime of the permease in the membrane (McKenna, E., Hardy, D., Pastore, J. C., and Kaback, H. R. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2969-2973). Thus, either the last turn of putative helix XII or the region immediately distal to helix XII is important for proper folding, and hence, activity and resistance to proteolysis. In an effort to determine whether this 3-4-amino acid sequence comprises the final turn of the last transmembrane helix of the permease or the beginning of the hydrophilic C-terminal tail, we deleted residues 401-417 and replaced amino acid residues 397-400 with either 4 Leu residues ("helix making") or Gly-Pro-Gly-Pro ("helix breaking"). Permease with 4 Leu residues at positions 397-400 is fully functional with respect to transport and completely stable, as judged by [35S]methionine labeling experiments. In marked contrast, permease with Gly-Pro-Gly-Pro at the same positions exhibits minimal activity and is unstable. The results imply that the amino acid sequence ... Val397Phe398Thr399 Leu400 ... in lac permease may comprise the last turn of transmembrane helix XII, rather than the beginning of the C-terminal tail.

Amino Acid Sequence↗
PubMed1991

Malignant transformation of aneurysmal bone cyst, with an analysis of the literature.

An 11-year-old girl had a lytic, benign-appearing, expansive lesion of the distal tibia radiologically interpreted as an aneurysmal bone cyst (ABC). Tissue from two extensive curettage procedures was also histologically diagnosed as ABC. Approximately 50 months after the onset of symptoms, and 28 months after her last curettage, a highly pleomorphic osteosarcoma developed. The patient had not received prior radiation therapy. The cases in the literature of possible malignant transformation of ABC are reviewed. The authors separate their case from telangiectatic osteosarcoma, and from "aneurysmal bone cyst-like osteosarcoma."

Bone Cysts↗
PubMed1991

Sequential truncation of the lactose permease over a three-amino acid sequence near the carboxyl terminus leads to progressive loss of activity and stability.

Previous experiments are consistent with the notion that residues 396-401 (... SVFTLS ...) at the carboxyl terminus of the last putative transmembrane helix of the lactose (lac) permease of Escherichia coli are important for protection against proteolytic degradation and suggest that this region of the permease may be necessary for proper folding. Stop codons (TAA) have now been substituted sequentially for amino acid codons 396-401 in the lacY gene, and the termination mutants were expressed from the plasmid pT7-5. With respect to transport, permease truncated at residue 396 or 397 is completely defective, while molecules truncated at residues 398, 399, 400, and 401, respectively, exhibit 15-25%, 30-40%, 40-45%, and 70-100% of wild-type activity. As judged by pulse-chase experiments with [35S]methionine, wild-type permease or permease truncated at residue 401 is stable, while permease molecules truncated at position 400, 399, 398, 397, or 396 are degraded at increasingly rapid rates. The findings indicate that either the last turn of putative helix XII or the region immediately distal to helix XII is important for proper folding and protection against proteolytic degradation.

Amino Acid Sequence↗
PubMed1991

Pigmented villonodular synovitis of the hip. A case report and review of the literature.

A 73-year-old patient, whose hip was completely destroyed by pigmented villonodular synovitis, was successfully treated by a total prosthetic replacement of this articulation. The etiopathogenesis of the illness is uncertain. Its' localization in the hip is, fortunately, a rare occurrence. It can be responsible for frequently extensive articular destruction which is even more dramatic when it affects young patients, whose average age is 35. Only early diagnosis permits conservative surgical treatment: total synovectomy associated with curettage of the foyers of osteolysis and their filling with bone grafts. If the destructive lesions are too extensive, an arthrodesis or replacement arthroplasty are proposed.

Aged↗
PubMed1991

Focal left temporal slow EEG activity is related to a verbal recent memory deficit in a non-demented elderly population.

Neuropsychological measures of memory and cognition and topographical quantitative EEG were obtained on 35 healthy, non-demented, right-handed, elderly subjects aged 60-81. All were free of medications which impair cognition. They were divided into a left temporal slow abnormality group (n = 9) and a control group (n = 26) on the basis of topographically normalized measures of both delta and theta activity for the left temporal lead T3. The group with left temporal slow activity was significantly deficient on measures of memory savings and memory losses derived from the Logical Memory (Story Recall) Test in the Wechsler Memory Scale--Revised. There were no significant differences between these two groups on the non-memory cognitive tasks. This predominant verbal recent memory deficit profile is reasonably similar to the neuropsychological deficit profile of very mildly demented Alzheimer patients. Because left temporal slow EEG activity is also the predominant EEG abnormality in mild Alzheimer patients, a prospective study should be done to determine if this abnormality in non-demented elderly subjects is most often a preclinical sign of Alzheimer's disease.

Aged↗
PubMed1990

Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia.

The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

Base Sequence↗
PubMed1990

Replication of HIV-1 in a wide variety of animal cells following phenotypic mixing with murine retroviruses.

Human T cells co-infected with the human immunodeficiency virus type 1 (HIV-1) and the xenotropic or dual-tropic mouse type C virus (MuLV) give rise, by phenotypic mixing, to progeny virus that can transfer HIV-1 into a wide variety of mammalian and avian cells. Differences in the extent of HIV-1 replication in these animal cells can be observed. Replication is best in human cells, but occurs substantially in cells from many animal species including mink, horse, and bush wallaby. Virus production in murine and avian cells is very limited. These results confirm that the major block to HIV-1 infection of animal cells is at the cellular surface but that intracellular regulation of viral replication is also involved. Moreover, an enhancement of HIV-1 cytopathic effects can be seen in human cells co-infected by MuLV. All these data suggest phenotypically mixed viruses might be useful for developing an animal model system for studying AIDS, and that the pathological expression of HIV-1 could be modified by the presence in cells of other retroviruses. They also indicate a potential mechanism by which HIV strains can be generated with an increased ability to spread in nature.

Acquired Immunodeficiency Syndrome↗