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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 595 records · Page 33Linked to original sources

Culture of PNKT-4B cells at invasion permissive and restrictive temperatures. I. Chromosomal analysis.

PNKT-4B is an aneuploid cell line derived from a herpesvirus-induced renal adenocarcinoma of Rana pipiens that displays restricted invasion at 21 degrees C or cooler and invasion at 23 degrees C through 28 degrees C. Metaphase chromosomes obtained from subcultures (passages 297; 345-347) grown at 18 degrees C or 28 degrees C were Giemsa stained or N-banded with acidic silver nitrate. Cells grown at 18 degrees C displayed a modal chromosome number of 41, while 28 degrees C cultures displayed a modal number of 40. The distribution of the chromosomes suggests that the two temperatures may be allowing growth of different subclonal populations. N-banding of chromosomes at both temperatures revealed an increase of active nucleolar organizer regions (NORs) over normal frog tissues, 2/2N. Analysis of 200 N-banded spreads from cells grown at each temperature revealed modal numbers of 9 NORs/cell and modal numbers of 6 NOR-containing chromosomes/cell. Nine specific NOR-containing chromosomes were identified and scored. Similar distributions were observed at 18 degrees C and 28 degrees C. The data imply that the modal number of PNKT-4B has shifted since it was first described, 39, and differs at invasion-permissive and -restrictive temperatures. Increased numbers of active NORs and alterations of NOR-containing chromosomes imply an amplification of rDNA over the amount in normal frog.

Adenocarcinoma↗

Controversies in the management of HIV-related illnesses.

The care of patients who have HIV infection requires technical competence, skill in clinical decision making, a commitment to continuing self-education, the ability to collaborate with medical and community-based service providers, and attention to the psychological and ethical aspects of patient care. General internists bring these attributes to their work and will be increasingly involved in meeting the challenges presented by the AIDS epidemic. Controversial issues in the management of HIV illness include: assessment and management of latent syphilis in patients with intercurrent HIV infection; risk assessment and postexposure zidovudine prophylaxis of health care workers after occupational accidents; determination of the risk of reactivation tuberculosis in HIV-infected individuals; and treatment or nontreatment of infections with the Mycobacterium avium complex in symptomatic patients. Patients illustrating these management problems are presented by progressive disclosure; the points made in discussion by a panel of general internists and AIDS specialists are presented.

AIDS Dementia Complex↗

Primary care and HIV disease.

Nearly one million Americans are infected with the human immunodeficiency virus (HIV). With the advent of increasingly effective therapy, including intervention early in the course of infection, there will be a growing need for physicians technically and attitudinally prepared to provide primary care for HIV-infected individuals. For any disease, however, determination of which physicians provide the bulk of care depends on several factors, including the prevalence and chronicity of the disease, the complexity, rate of change, and toxicity of therapy, and the socioeconomic characteristics of patients with the disease. General internists will clearly constitute a large part of the pool of practitioners caring for HIV-infected patients, especially in the earlier stages of infection. It seems reasonable to expect every general internist to be competent in four aspects of HIV care: counseling about transmission and prevention; the proper administration and interpretation of diagnostic tests; monitoring and care of patients in early stages of infection; and recognition of complications of advanced infection for proper management or referral. Academically based generalists will have a major role in research, teaching, and patient care in the AIDS epidemic. The organization and delivery of primary and specialty care for HIV-infected people in future years will continue to evolve with changes in therapy and in the demography of the epidemic.

Acquired Immunodeficiency Syndrome↗

Quantitative recovery of Burkholderia pseudomallei from soil in Thailand.

Melioidosis is common in north-eastern Thailand, but is reported rarely from the adjacent areas of central Thailand, although rice farming is common to both regions. Quantitative soil cultures for Burkholderia pseudomallei were therefore prepared on 12 rice farms in both regions. B. pseudomallei was isolated from a similar proportion of rice fields in the central region (6/12) and in the north-east (7/12). Within the culture-positive sites, the number of B. pseudomallei colony-forming units (cfu) per mL of soil/water supernatant was significantly higher in the north-east (median 230 cfu/mL; range 1-17,000) than in the central region (median 10 cfu/mL; range 1-600). As bacterial counts in the soil are probably related to the risk of developing melioidosis, differences in exposure to B. pseudomallei probably contribute to the considerable differences in the incidence of this disease between these 2 adjacent regions.

Burkholderia pseudomallei↗

A prospective comparison of co-amoxiclav and the combination of chloramphenicol, doxycycline, and co-trimoxazole for the oral maintenance treatment of melioidosis.

An open randomized comparison of the oral 'conventional' regimen (combination of chloramphenicol, cotrimoxazole and doxycycline) and co-amoxiclav for the maintenance treatment of melioidosis was conducted in Ubon Ratchatani, north-eastern Thailand, between 1989 and 1992. The total antibiotic treatment duration was 20 weeks. Of 101 patients followed, 10 (10%; 95% confidence interval [CI] 4.9-17.5%) subsequently relapsed: 2 of 52 patients (4%) in the oral 'conventional' group, and 8 of 49 patients (16%) receiving oral co-amoxiclav. This compares with a relapse rate of 23% in our previous study of 8 weeks' total therapy. Only 50% of patients complied with the 20 weeks' treatment regimen and poor compliance proved the most significant risk factor for subsequent relapse (relative risk [RR] 4.9, 95% CI 1.2-20.3). Neither the presence of known underlying disease nor choice of initial parenteral treatment was significantly associated with a higher risk of relapse. Co-amoxiclav is safer and better tolerated, but may be less effective (RR of relapse 0.4, 95% CI 0.2-1.2) than the oral 'conventional' regimen. The minimum duration of total treatment with either regimen should be 12-20 weeks, depending on clinical progress.

Adolescent↗

Isolation of Pseudomonas pseudomallei from soil in north-eastern Thailand.

In order to optimize the recovery from soil of Pseudomonas pseudomallei, the cause of melioidosis, 3 selective broths were compared. A basal salt solution containing L-threonine (TBSS) performed significantly better than trypticase soy broth containing crystal violet and colistin 50 mg/L (CVC50), both in isolation rate and suppression of overgrowth of other organisms, but the addition of colistin to TBSS gave the best results overall. In a survey in north-eastern Thailand, P. pseudomallei was recovered from 114 (68%) of the 167 sites tested. A detailed study of a single rice farm showed that the isolation rate increased with depth of soil sample, and P. pseudomallei could still be isolated during the dry season, although only from moist soil in areas where other crops were cultivated and around the water source.

Animals↗

Oral fluoroquinolones for maintenance treatment of melioidosis.

Ciprofloxacin (20 mg/kg/d) or ofloxacin (12 mg/kg/d) given for a median of 15 weeks (range 12-40) were used for maintenance treatment of 57 adult patients with melioidosis. The median duration of follow-up in the 45 patients who complied with treatment and were followed for at least 6 months was 28 months (range 6-65). Fluoroquinolone treatment was well tolerated. There were 13 treatment failures (5 failures to respond, 8 relapses), a failure rate of 29% (95% confidence interval 17-43%). The median time to treatment failure was 7 months (range 2-26). These results are inferior to those with courses lasting 20 weeks of amoxycillin/clavulanic acid or the combination of chloramphenicol, doxycycline and trimethoprim/sulphamethoxazole, and suggest that the fluoroquinolones should be reserved as third line agents, and not used for the maintenance treatment of melioidosis unless there is resistance to, or intolerance of, the other available antimicrobial compounds.

Adolescent↗

Short courses of ofloxacin for the treatment of enteric fever.

Typhoid fever continues to be a major public health problem in tropical countries, exacerbated in recent years by the spread of multi-drug resistant strains of Salmonella typhi. Short treatment courses of fluoroquinolones are effective, and have the advantage of reduced cost and increased compliance, but the optimal length of treatment is unknown. In an open, randomized comparison, 107 adults with uncomplicated enteric fever (95 of whom had positive blood cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin, 15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the same in the 2 treatment groups (97 h). There were 7 treatment failures, one in the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected with nalidixic acid resistant strains of S. typhi had treatment failures, compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001; relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin for 2 or 3 d is equally effective in adults with uncomplicated enteric fever caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and management of nalidixic acid resistent typhoid needs further investigation.

Adult↗

Community-acquired septicaemia in southern Viet Nam: the importance of multidrug-resistant Salmonella typhi.

In a prospective study conducted between mid 1993 and 1994, 437 adults and children were admitted with community-acquired septicaemia to an infectious diseases hospital in southern Viet Nam. Gram-negative aerobes accounted for 90% of isolates and were predominantly Salmonella typhi (67%), Sal. para-typhi A (3%), Escherichia coli (10%), and Klebsiella spp. (5%). Other Salmonella spp. (1%), Pseudomonas aeruginosa (1%), Neisseria meningitidis (0.5%) and Haemophilus influenzae (0.2%) were uncommon. Staphylococcus aureus (5.5%) and Streptococcus pneumoniae (2%) were the most common Gram-positive isolates. Patients with enteric fever were younger (median age 16 years, range 1-63) than the other patients (median age 43 years, range 1-88) (P < 0.001) and had a lower mortality rate (0.3% vs. 23%; relative risk 69.5, 95% confidence interval 9.5-507.8; P < 0.0001). Over 70% of the Sal. typhi isolated were multi-drug-resistant, and 4% were resistant to nalidixic acid. Multidrug-resistant Sal. typhi is a major cause of community-acquired septicaemia in Viet Nam.

Adolescent↗

Reliability of blood pressure, heart rate, and Doppler-derived hemodynamic measurements during exercise.

Doppler echocardiography of aortic blood flow, heart rate, and blood pressure represent noninvasive methods for evaluation of the hemodynamic effects of pharmacologic agents or other stimuli during rest and exercise. In this study the reliability of continuous-wave Doppler echocardiography for detecting the effects of various interventions on left ventricular systolic function during exercise was assessed. The reliability of Doppler measurements was compared with that found for measurements of simultaneously obtained heart rate and blood pressure. Exercise treadmill testing was performed at 0, 2, 4, 6, and 8 hours in 18 healthy male subjects. All measurements were performed at rest and during the last half of each exercise stage. Reliability of peak modal velocity, peak aortic blood flow acceleration, heart rate, and blood pressure was measured by the intraclass correlation coefficient (ICC) at each stage. ICC reliability of greater than 0.75 is considered excellent, 0.4 to 0.75 fair to good, and less than 0.4 poor. The reliability of all Doppler-derived parameters, heart rate, and blood pressure improved with increasing stage of exercise. Peak modal velocity, peak acceleration, heart rate, and manually obtained systolic blood pressure had ICCs of 0.75 or greater by stage 3. The reliability of Doppler-derived aortic blood flow parameters was good or excellent at rest and advanced stages of exercise. Continuous-wave Doppler echocardiography is a reliable method for performing studies to assess the effects of interventions on cardiovascular function during exercise.

Adult↗