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Biomedical subjects

M McDonald

Publications and source records attributed to M McDonald.

At least 73 records · Page 4Linked to original sources

Comparative efficiency of feline immunodeficiency virus infection by DNA inoculation.

Direct inoculation of genetic material in DNA form is a novel approach to vaccination that has proved efficacious for a number of viral agents. We are interested in the potential of this approach for the delivery of vaccines based on attenuated or replication-defective retroviruses. Toward this goal, we tested the effect of intramuscular inoculation of a plasmid containing the entire genome of feline immunodeficiency virus (FIV-Petaluma, F14 clone). DNA delivery was compared with intramuscular or intraperitoneal inoculation of virus reconstituted from the same molecular clone. The outcome was monitored by serological analysis and quantitative virus load determination over a 31-week period. DNA inoculation was found to be a reliable means of infection, although seroconversion and the rise in PBMC virus load were delayed relative to intramuscular or intraperitoneal inoculation of virus. At 31 weeks, similar levels of proviral DNA were detected in central lymphoid tissue of all infected animals. In conclusion, DNA inoculation of proviral DNA will be of use as a novel method of cell-free virus challenge and may have further potential for the delivery of lentiviral vaccines.

Animals↗

Comparative genomic hybridization reveals previously undescribed amplifications and deletions in the chronic myeloid leukemia-derived K-562 cell line.

We used comparative genomic hybridization (CGH) to identify a number of previously undescribed chromosomal imbalances in K-562, a spontaneously transformed cell line originally derived from leukemic cells of a chronic myeloid leukemia (CML) patient in blast crisis. Noteworthy were a discrete amplification in band 13q31, increased copy number of chromosome arms 1q, 5p, 6p, and 16q, and loss of material from 8p, 9p, 10q, and 17p. Amplification within bands 9q34 and 22q11.2 was consistent with previous descriptions of increased copy number of the CML-specific 5'BCR-3'ABL fusion gene in K-562. However, amplification of a large distal segment, 9q31-->9q34, mostly proximal to the ABL locus, was unexpected and is unlikely to be related to BCR-ABL recombination. Previous karyotype studies are reviewed in detail and compared with the CGH findings.

Female↗

Minimally invasive management of low-grade and benign gastric tumors.

BACKGROUND: Benign gastric tumors and tumors of low-grade malignancy can be safely removed laparoscopically. METHODS: Seven patients were considered candidates for laparoscopic resection of gastric tumors. Inclusion criteria included small tumor size (less than 6 cm), exophytic or endophytic tumor morphology, and benign characteristics. Indications for surgical intervention included bleeding, weight loss, and need for tissue diagnosis. Patients ranged in age from 38 to 70. There were five female and two male patients. All patients underwent preoperative upper GI endoscopy. The procedures were performed using a four- or five-port technique. An Endo-GIA (US Surgical Company, Norwalk, Connecticut) was used to amputate those tumors located on the serosal surface of the stomach. Tumors on the mucosal surface were exposed via a gastrotomy, then likewise amputated using an Endo-GIA. The gastrotomy closure was then either hand sewn or stapled. Operating time ranged from 95 to 225 min. RESULTS: Final pathologic diagnoses included lipoma, lymphoma, leiomyoma, and leiomyosarcoma. There was a 28% conversion rate. There were no complications. Length of postoperative stay ranged from 4 to 7 days. There have been no tumor recurrences in 6-38-month follow-up. CONCLUSIONS: Minimally invasive management of benign and low-grade gastric tumors can be performed safely with excellent short- and long-term results.

Adult↗

Comparison of dietary risk factors for cardiovascular disease in African-American and white women.

OBJECTIVE: To compare African-American and white women's knowledge, attitudes, and energy and nutrient intakes related to cardiovascular disease risk. DESIGN: The 1989 through 1991 Continuing Survey of Food Intakes by Individuals and the Diet and Health Knowledge Survey (DHKS). SUBJECTS: A nationally representative sample of 2,684 white and 449 African-American women who completed the DHKS and provided 3 days of dietary information. STATISTICAL ANALYSES PERFORMED: Comparisons between groups were made using t tests and chi 2 analyses. Analysis of covariance was used to adjust for age, percentage of poverty, and education. RESULTS: Significant differences in dietary risk for cardiovascular disease were identified. White women consumed significantly less cholesterol and more potassium than African-American women. African-American women had significantly lower knowledge scores, but they were more likely than white women to indicate that their diets should be lower in fat and salt and to consider nutrition very important when shopping. White women had more positive attitudes toward the impact of diet on health than African-American women. Accounting for differences between the groups in age, education, and income explained few differences between the groups. APPLICATIONS: This study identified differences in nutrient intake, knowledge, and attitudes about diet and health that can influence the willingness and ability of women to choose foods for a more healthful diet. Dietitians can use these findings to target strategies for changing behavior. For example, many African-American women acknowledge the need to change their current diets, so dietitians can help them design implementation plans or specific action plans to accomplish needed changes.

Black or African American↗

Pain syndromes and etiologies in ambulatory AIDS patients.

Ambulatory AIDS patients participating in a quality of life study were recruited for an assessment of pain syndromes. Of 274 patients with pain, 151 (55%) consented to the assessment which included a clinical interview, neurologic examination, and review of medical records. The number, type, and etiology of pains were evaluated in terms of risk factors, age, sex, CD4+ lymphocyte count, and performance status. The average number of pains per patient was 2.7 (range, 1-7), yielding a total of 405 pains. The most common pain diagnoses were headache (46% of patients; 17% of all pains), joint pain (31% of patients; 12% of pains), pain due to polyneuropathy (28% of patients; 10% of pains), and muscle pain (27% of patients; 12% of pains). Pathophysiology was inferred for all pain syndromes (except for headache), 45% of pain syndromes were somatic in nature, 15% were visceral, 19% were neuropathic, and 4% were unknown, psychogenic, or idiopathic; 17% of pains were classified as headache, hence pathophysiology could not be determined. Pain resulted from diverse etiologies, including the direct effects of HIV/AIDS-related conditions (30%) pre-existing unrelated conditions (24%), and therapies for HIV/AIDS and related conditions (4%). The latter category, pain related to HIV therapies, occurred in 11% of patients. In 37% of the pains, the etiology could not be determined from the information available. In univariate analyses, lower CD4+ cell counts were significantly associated with polyneuropathy (P < 0.05) and headache (P < 0.05), and female gender was significantly associated with the presence of headache (P < 0.05) and radiculopathy (P < 0.001). These data confirm the diversity of pain syndromes in AIDS patients, clarify the prevalence of common pain types, and suggest associations between specific patient characteristics and pain syndromes. The large proportion of patients who could not be given a diagnosis underscores the need for a careful diagnostic evaluation of pain in this population.

Adolescent↗

Bradykinin-induced venodilation is not different in blacks.

AIMS: The aim of this study was to determine whether young, normotensive blacks who have been recently demonstrated to have a venodilator response to isoprenaline decreased compared with whites, also have an decreased vasodilatory response to bradykinin. METHODS: Eleven black and 11 white subjects were studied. Full dose-response curves to bradykinin (dosing range 0.5-500 ng min-1) were generated in hand veins preconstricted with phenylephrine (dosing range 20-6800 ng min-1). RESULTS: The groups had a similar maximal response to bradykinin (57.6 +/- 32.2% vs 67.8 +/- 49.3%, P = NS 95% confidence interval for the difference (CI): -47.3, 26.8). Also, the log of the dose that produced half maximal response to bradykinin was similar for the two groups (0.89 +/- 0.58 vs 0.78 +/- 0.61 ng min-1, P = NS, 95% CI: -0.42, 0.64). There was no difference between the two groups in the log dose of phenylephrine necessary to produce 80% constriction of the hand vein. CONCLUSION: Diminished vasodilatory response to endothelium-derived relaxing factor (EDRF) does not seem to be associated with the increased prevalence of hypertension in blacks.

Adult↗

Modeling drug residue uptake by eggs: yolks contain ampicillin residues even after drug withdrawal and nondetectability in the plasma.

The present study was conducted to determine whether: 1) preovulatory yolks may be an important storage depot for drug residues in eggs laid days to weeks after drug withdrawal; and 2) the prediction model based on the pattern of drug incorporation in developing yolks is predictive of the pattern of residues contained in the sequence of eggs laid during and after drug withdrawal. To test these possibilities, 24 hens were dosed for either 1, 2, or 3 d with ampicillin, and the content and pattern of residues in laid eggs were evaluated during and after dosing. Hens were bled 24 h after the final dosing, and plasma ampicillin concentrations were determined. Ampicillin was used in this study because it has an extremely short plasma halflife in laying hens that limits additional drug transfer after drug withdrawal. Ampicillin concentrations were not detectable in plasma from hens injected with ampicillin for either 1, 2 or 3 d (assay sensitivity of 0.6 ng/ml or 0.6 ppb). Hens from all three injection groups produced eggs containing detectable ampicillin residues for 6 d after the last injection. These data demonstrate that drug residues are contained in eggs laid a number of days after drug withdrawal. Because plasma ampicillin was not detectable even 24 h after final dosing, the majority, if not all, of the incurred ampicillin residues contained in eggs laid after drug withdrawal were due to incorporation and storage of drug in preovulatory yolks during the dosing period. Additionally, accounting for ampicillin's stability, our model is predictive of the pattern of residues contained in eggs. These data emphasize the importance of transfer and storage of drugs in preovulatory yolks as a significant contributing mechanism for the production of incurred drug residues in eggs.

Ampicillin↗

The epidemiology of methicillin-resistant Staphylococcus aureus: surgical relevance 20 years on.

Despite vigorous attempts at eradication over the last 20 years, methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major nosocomial pathogen in Australian acute care institutions. The epidemiology of hospital spread is now well characterized; infected and colonized patients provide the primary reservoirs, and transmission is mainly via hospital staff. The MRSA remains endemic in most of Australia's large urban teaching hospitals; occasional outbreak also occur, especially in intensive care areas. The level of MRSA infection is often indicative of the total rate of nosocomial infection within an institution and may reflect overcrowding, heavy workloads and under-staffing of wards. Standard precautions, isolation and cohorting of infected and colonized patients, screening of staff, hand washing campaigns, nasal eradication policies and increased staff education have all been tried, with variable success. There is no universal formula; local problems require local solutions plus commitment of local resources. Preventing surgical infection with MRSA requires the application of surgical first principles, and the routine use of vancomycin for prophylaxis is not recommended.

Australia↗

Ambulatory electrocardiography for the detection of pacemaker lead failure.

The suboptimal performance of some polyurethane bipolar pacing leads has highlighted concern about the optimal method of monitoring pacemaker lead performance. Since the manifestations of premature lead failure may be initially intermittent, we hypothesized that ambulatory electrocardiography (AECG) would be a more sensitive tool for the detection of pacing lead failure compared to increased pacemaker clinic surveillance. Since the Medtronic safety alerts on the 4012, 4082, and 4004 leads, we have followed 261 patients by serial AECG and 165 patients by increased pacemaker clinic surveillance. Lead failures were identified in 75 patients: 68 in the AECG group (31%) and 7 in the clinic group (4%, P < 0.001). Repeat AECG confirmed the lead failure in 38 (97%) of 39 patients in which it could be done. Pacing lead failure documented by AECG could be confirmed by a subsequent clinic assessment in only 15 (25%) of 60 patients evaluated (P < 0.001). The actuarial survival of the 4012 lead was significantly lower in the AECG group compared to the clinic group (56% vs 87% survival at 8 years, P < 0.002). Similar trends were observed for the 4082 and 4004 leads. AECG is a more sensitive method of surveillance for pacemaker lead function compared to pacemaker clinic assessment. AECG should be incorporated into the routine follow-up of pacemaker patients.

Aged↗

The effect of anticipatory discharge orders on length of hospital stay in staff pediatric patients.

Effective discharge planning should serve to reduce length of stay (LOS) and lower readmission rates. A combined prospective/retrospective study was undertaken to assess the effectiveness of anticipated discharge order forms in decreasing LOS for staff pediatric patients. Resident physicians provided advance notice of the planned discharge date to nursing staff and patient family members. Patient selection was random, and the data were collected prospectively. These subjects were matched with patients for whom the order form was not used, and the data was collected retrospectively. Matching variables included: diagnosis, age, gender, race, and method of payment. There were 103 matched pairs. LOS was collapsed into low and high categories. There was a significant difference when comparing subject groups (chi 2 = 8.5; P = 0.005). Whereas only 14% of experimental patients were categorized as high LOS, 32% of control patients were classified as such. Physician prediction of discharge date helped decrease patient LOS.

Adolescent↗

Mutation in the influenza virus neuraminidase gene resulting in decreased sensitivity to the neuraminidase inhibitor 4-guanidino-Neu5Ac2en leads to instability of the enzyme.

We previously isolated a variant of the influenza virus NWS/G70C, with a decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino-Neu5Ac2en in vitro, which has a mutation in one of the conserved residues of the neuraminidase Glu 119 to Gly. Despite the mutation, purified neuraminidase demonstrated the same specific activity as the parent neuraminidase. In contrast, characterization of a similar mutant by another group revealed a low specific activity of the enzyme. We confirm here that the specific activity of our variant is the same as that of the parent, but report that this mutation makes the enzyme inherently unstable, at high and low temperatures, either on the virion or as purified neuraminidase. Thus, for a valid determination of specific activity the concentration of native NA needs to be determined at the time of enzyme assay. Structurally, the instability may be partially explained by the introduction of a side chain (Gly), which carries a greater entropy penalty in condensation of the structure from the unfolded to the folded state and this, together with the loss of stabilizing interaction between Glu 119 and its neighbors in the active site, is not compensated for by the water molecule occupying the position of the carboxylate group (6).

Animals↗

BCR gene recombines with genomically distinct sites on band 11Q13 in complex BCR-ABL translocations of chronic myeloid leukemia.

We have analysed a cloned 11q13/3'BCR junction fragment, one recombination product of a complex t(9;11;22) translocation in a patient with chronic myeloid leukemia. 3'M-Bcr recombined with chromosome band 11q13 at a specific point between two Alu elements lying in opposite orientation. We present new molecular data comparing the genomic location of the 11q13 breakpoint in our patient with that of one other recently reported to lie within the GSTP1 gene. This is the first time that specific breakpoint sites within a chromosomal region highly involved in complex Ph translocations have been relatively mapped. These early results argue against a precise site in 11q13 with which M-Bcr preferentially recombines and favour instead a larger recombination-prone domain. Both of the 11q13 breakpoint regions show Alu repeat elements in close proximity to the site of recombination.

Base Sequence↗

Cytogenetic and molecular analysis of inv dup(15) chromosomes observed in two patients with autistic disorder and mental retardation.

A variety of distinct phenotypes has been associated with supernumerary inv dup(15) chromosomes. Although different cytogenetic rearrangements have been associated with distinguishable clinical syndromes, precise genotype-phenotype correlations have not been determined. However, the availability of chromosome 15 DNA markers provides a means to characterize inv dup(15) chromosomes in detail to facilitate the determination of specific genotype-phenotype associations. We describe 2 patients with an autistic disorder, mental retardation, developmental delay, seizures, and supernumerary inv dup(15) chromosomes. Conventional and molecular cytogenetic studies confirmed the chromosomal origin of the supernumerary chromosomes and showed that the duplicated region extended to at least band 15q13. An analysis of chromosome 15 microsatellite CA polymorphisms suggested a maternal origin of the inv dup(15) chromosomes and biparental inheritance of the two intact chromosome 15 homologs. The results of this study add to the existing literature which suggests that the clinical phenotype of patients with a supernumerary inv dup(15) chromosome is determined not only by the extent of the duplicated region, but by the dosage of genes located within band 15q13 and the origin of the normal chromosomes 15.

Adolescent↗

Community-wide HIV counselling and testing in central Massachusetts: who is retested and does their behavior change?

HIV counselling and testing was provided to 4267 individuals between September 1987 and June 1992 at a multi-site program, including community clinics, drug treatment programs, and a men's prison in central Massachusetts. Half of those tested reported the risk behaviors targeted by the programs: injection drug use (38.1%) and sexual contact with a drug injector (12.6%). The objectives of this study were to examine 1) factors associated with repeat HIV testing among these initially seronegative, and 2) behavior change following counselling and testing. Initially 7.4% were HIV positive, and 12.4% of those testing negative were retested within one year. Risk behavior was the only strong independent predictor of retesting (odds ratios of 3.8 and 4.2 for men reporting sex with men and recent drug injectors, respectively). Changes in risk behaviors between the time of the initial test and the second test were assessed (n = 207). Among those who continued to inject drugs at follow-up there was a reduction in the percent visiting shooting galleries (p = 0.05); no other significant behavior changes were reported. While selection bias may be responsible in part for the minimal behavior change observed, continued monitoring of risk behavior and counselling are warranted.

Adolescent↗

Fungal bezoar and bladder rupture secondary to candida tropicalis.

Candidal urinary tract infections typically occur in a host with compromised immune function. Although usually associated with aerobic bacterial infections, emphysematous cystitis occasionally complicates fungal infections of the lower urinary tract, especially in diabetics. Another uncommon occurrence is formation of a "fungus ball" leading to obstructive uropathy. We present a case of bladder rupture in a patient with emphysematous cystitis and obstructing fungal bezoar caused by Candida tropicalis. Various factors predispose to fungal urinary tract infection, including diabetes mellitus, neurogenic bladder, antibiotic usage, and the presence of an indwelling urinary catheter.

Adult↗