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Biomedical subjects

R B Roberts

Publications and source records attributed to R B Roberts.

At least 55 records · Page 3Linked to original sources

Regression of renal hypertrophy and elevated renal Na+,K+-ATPase activity after insulin treatment in streptozotocin-diabetic rats.

The effect of insulin treatment on the renal hypertrophy and elevated renal Na+,K+-ATPase activity in rats with streptozotocin (STZ)-induced diabetes was examined. Rats with STZ-diabetes of 6- to 8-week duration had significantly lower body weights, higher plasma and urinary glucose concentrations, greater urinary volumes, increased kidney weights, and increased kidney/body weights and protein/kidney weight ratios compared to those in saline-citrate-injected controls. Specific Na+,K+-ATPase activity per mg protein in both cortical and outer medullary kidney homogenates was significantly elevated in diabetic vs. control animals, as was total renal Na+,K+-ATPase activity. One week of insulin treatment returned elevated plasma glucose, urinary volume, the protein/kidney weight ratio, and cortical and outer medullary Na+,K+-ATPase activity per mg protein to control values. Kidney weights and kidney/body weight ratios of diabetic animals remained elevated, as did absolute total renal Na+,K+-ATPase activity. After 3 weeks of insulin treatment, kidney weight and total renal Na+,K+-ATPase activity in diabetic animals returned to control values, but body weights remained lower than those in the controls, resulting in continued elevation of kidney/body weight ratios in the diabetic animals. The concurrent regression of both renal hypertrophy and elevated Na+,K+-ATPase activity to normal levels after insulin treatment of STZ-diabetic animals implicates renal growth rather than a direct effect of insulin as the primary factor controlling elevation and regression of Na+,K+-ATPase activity in the diabetic kidney. This finding demonstrates that the effect of renal hypertrophy can outweigh the intrinsic effects of insulin on an important renal transport system and that this effect may be as important as lack of hormone in determining the renal physiological responses in the disease. It is suggested that the increased renal tubular Na+,K+-ATPase activity is a key component of the renal hypertrophy and hyperfunction seen in diabetes.

Animals↗

Relation between the presence of echocardiographic vegetations and the complication rate in infective endocarditis.

M-mode and two-dimensional echocardiograms of 77 patients with infective endocarditis were examined to determine if presence and/or size of vegetations on echocardiogram were predictive of morbidity and mortality. Patients with (n = 43) or without (n = 34) vegetations on echocardiogram did not differ significantly in the proportions developing congestive heart failure (23 of 43 or 53% vs 12 of 34 or 35%) or emboli (11 of 43 or 24% vs 6 of 34 or 18%), whereas a slightly lower proportion of those with vegetations required surgery (5 of 43 or 12% vs 7 of 34 or 21%) or died (3 of 43 or 7% vs 4 of 34 or 12%). No significant relationship was found between vegetation size and the frequency of complications, the need for surgery, or death. In contrast, patients whose echocardiograms demonstrated premature mitral valve closure or chordal or cusp rupture had a significantly higher incidence of heart failure (10 of 13 or 77% vs 22 of 60 or 37%, p less than 0.003) and surgery (3 of 13 or 23% vs 7 of 60 or 12%, p less than 0.05). We conclude that: the presence of vegetation on the initial echocardiogram is not predictive of the clinical course in infective endocarditis; vegetation size does not predict complications, need for surgery, or death; but valve cusp or chordal rupture and/or premature mitral valve closure are associated with congestive heart failure and the need for surgery.

Adolescent↗

Complications of mitral valve prolapse. Disproportionate occurrence in men and older patients.

To determine factors influencing the strength of association between mitral valve prolapse and mitral regurgitation, ruptured chordae tendineae, and infective endocarditis, the prevalence of mitral prolapse in patients with disease was compared with both clinical and population control groups. The prevalence of mitral valve prolapse was 4 percent among population and clinical control groups (eight of 196 and 84 of 2,146, respectively) and was significantly higher (p less than 0.001) in patients with endocarditis (11 of 67, 16 percent), mitral regurgitation (17 of 31, 55 percent, and ruptured chordae (27 of 43, 63 percent). Odds ratios for complications in persons with mitral valve prolapse ranged from 4.6 for endocarditis to 41.4 for ruptured chordae in overall analyses, and from 6.8 for endocarditis to 53.0 for ruptured chordae based on age- and sex-matched case-control triplets (p less than 0.001 for each). All complications occurred disproportionately in men with mitral valve prolapse, in whom odds ratios ranged from 2.5 to 7.4 compared with an additional control group of unselected subjects with mitral valve prolapse. Compared with this control group, patients with mitral valve prolapse and endocarditis were slightly more likely to have a previously known heart murmur (odds ratio 3.2, difference not significant) but significantly more likely to have murmurs at the time of evaluation (odds ratio 8.5, p less than 0.01). Patients with mitral valve prolapse and mitral regurgitation and ruptured chordae tendineae were also significantly older than the unselected subjects with mitral valve prolapse (48 +/- 14 and 55 +/- 16 versus 38 +/- 14 years, p less than 0.005 for both). The concentration of risk of endocarditis in men with mitral valve prolapse and patients with antecedent murmur suggests that antibiotic prophylaxis is warranted in these groups but not in women without a murmur of mitral regurgitation.

Adolescent↗

Enzyme-linked immunosorbent assay for the detection of antibodies to nutritionally variant streptococci in patients with endocarditis.

The viridans streptococci are responsible for 50%-55% of microbial endocarditis. Among these varied species, the nutritionally variant streptococci (NVS) have recently been associated with culture-negative endocarditis and are responsible for 5%-10% of all streptococcal endocarditis. The isolation and identification of these bacteria has been hampered by the extremely fastidious nature of their growth requirements as well as by their slow growth rate. In addition, their antibiotic sensitivity varies greatly, a characteristic leading to a higher rate of morbidity and mortality than is found in patients with non-NVS endocarditis. For these reasons sera from patients with NVS endocarditis were examined for antibodies to the NVS serotype I antigen by using an enzyme-linked immunosorbent assay. Seventy-four percent of patients with NVS endocarditis had elevated titers to this antigen. None of the sera from controls and only 6.7% of the sera from patients with non-NVS streptococcal endocarditis showed increased titers. These results indicate that antibody to the NVS serotype I antigen can serve as a marker for NVS endocarditis.

Antibodies, Bacterial↗

Antimicrobial therapy of experimental endocarditis caused by nutritionally variant viridans group streptococci.

Rabbits with nutritionally variant viridans group streptococcal experimental endocarditis were treated three times daily for 3 days with procaine penicillin (1.2 X 10(6) U) alone or together with low-dose streptomycin (2 mg/kg), high-dose streptomycin (8 mg/kg), low-dose gentamicin (0.32 mg/kg), or high-dose gentamicin (1.05 mg/kg). The mean 0.5-h serum concentrations of streptomycin were 5.3 and 22.5 micrograms/ml in the low- and high-dose group, respectively, and the concentrations of gentamicin were 0.7 and 2.5 micrograms in the low- and high-dose groups, respectively. The combination of procaine penicillin with each dose of aminoglycoside was significantly more effective (P less than 0.001) than was procaine penicillin alone. In combination with procaine penicillin, the higher dose of streptomycin was significantly more effective (P less than 0.02) than the lower dose of streptomycin. The higher dose of streptomycin was not significantly more effective than either dose of gentamicin. The results of treatment with the high or low dose of gentamicin were virtually identical.

Animals↗

Mycobacterium avium-M. intracellulare isolates from patients with or without acquired immunodeficiency syndrome.

Susceptibility testing and serotyping were performed on 57 isolates of Mycobacterium avium-M. intracellulare from patients with acquired immunodeficiency syndrome (AIDS) and 75 isolates from patients without AIDS. Susceptibility patterns and serotypes of AIDS isolates were significantly different from those of non-AIDS isolates. These results may partially explain the poor therapeutic response of M. avium-M. intracellulare infections in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Comparison of ceforanide and cephalothin prophylaxis in patients undergoing total joint arthroplasty.

One hundred one patients undergoing total hip and knee arthroplasty were randomly assigned to receive either two 1 gm doses of ceforanide or five doses of cephalothin perioperatively. Simultaneous plasma and cancellous bone specimens were obtained intraoperatively and assayed for antibiotic concentration. Ceforanide plasma and bone levels remained sustained over six hours. Cephalothin plasma and bone levels obtained three to four hours post administration were 91% lower than levels obtained one hour post-dose. Patients were examined for infection for up to 18 months following surgery. None of the patients developed an infected implant. The sustained plasma and bone levels achieved with ceforanide obviate the need for intraoperative dosing necessary with other agents.

Adult↗

Patients at risk for AIDS-related opportunistic infections. Clinical manifestations and impaired gamma interferon production.

We studied 81 men (79 homosexuals and 2 drug abusers) with persistent lymphadenopathy to determine whether those at risk for AIDS-related opportunistic infections could be identified prospectively. (Sixty-nine of 76 [91 per cent] had antibodies to human T-cell lymphotropic virus Type III [HTLV-III], and 76 of 79 [96 per cent] had abnormal T4/T8 cell ratios.) During the follow-up period (mean +/- S.E.M., 12.9 +/- 0.5 months; range, 8 to 19), infections developed in none of 38 patients with lymphadenopathy alone and in only 1 of 15 (7 per cent) with antecedent herpes zoster infection; however, 13 of 28 (46 per cent) with lymphadenopathy accompanied by constitutional symptoms or oral candidiasis or both had opportunistic infections within the follow-up period. Among the results of various T-cell assays, only antigen-stimulated lymphocyte proliferation and gamma interferon generation, which were absent or barely measurable in those in whom AIDS ultimately developed, were of prognostic value. T cells from 15 patients, 11 of whom had constitutional symptoms or thrush, failed to generate antigen-induced gamma interferon; infections developed in 10 of these 15 (67 per cent) within a mean of 8.2 months. These results suggest that patients with AIDS-related complex who are at risk for opportunistic infections within a year can be identified by correlating clinical manifestations with antigen-stimulated T-cell responses--in particular, with the production of gamma interferon.

Acquired Immunodeficiency Syndrome↗

Production of and in vitro response to interleukin 2 in the acquired immunodeficiency syndrome.

To test the hypothesis that deficient interleukin 2 (IL-2) secretion may underlie the impaired capacity of T cells from patients with Acquired Immunodeficiency Syndrome (AIDS) and the AIDS-related complex (ARC) to generate the macrophage-activating lymphokine, gamma interferon (IFN-gamma), we used five specific microbial antigens to examine IL-2 production. Mononuclear cells from only one of 32 (3%) AIDS patients secreted normal levels of IL-2, and 21 (66%) failed to produce any detectable IL-2. For 36 ARC patients, IL-2 generation was normal in nine (25%) and absent in 11 (31%). Given these results, recombinant (r) IL-2 was tested for its capacity to stimulate or enhance IFN-gamma production. rIL-2 (10 U/ml) alone stimulated cells from controls, ARC, and AIDS patients to secrete 93 +/- 25, 99 +/- 33, and 7 +/- 3 U/ml of IFN-gamma, respectively. rIL 2 (10 U/ml) plus antigen induced no change in mean IFN-gamma levels for controls, a 4.4-fold increase for 17 AIDS patients (16 +/- 16 vs. 71 +/- 21 U/ml), and a 7.2-fold increase (18 +/- 5 vs. 130 +/- 27 U/ml) for 19 ARC patients with abnormal IFN-gamma generation to antigen alone. Individual responses indicated that six of the 17 (35%) AIDS patients with opportunistic infections and 12 of the 19 (63%) with ARC were apparent responders to 10-100 U/ml of rIL-2. These results (a) document profound impairment in antigen-induced IL-2 secretion by AIDS and ARC T cells, (b) indicate that, in vitro, mononuclear cells from certain patients can respond to rIL-2 with enhanced IFN-gamma production, and thus (c) suggest that in selected patients rIL-2 might have a potentially beneficial therapeutic (AIDS) or prophylactic (ARC) effect against opportunistic infections.

Acquired Immunodeficiency Syndrome↗

Salmonella infections in patients with the acquired immunodeficiency syndrome.

Defects in T-cell function have been seen in patients with the acquired immunodeficiency syndrome. Although the cellular immune system plays a key role in host defense against Salmonella, there have been no detailed reports of salmonellosis in patients with this syndrome. We report our experience with salmonella infections in six patients. Salmonellosis in these patients was unusually severe, characterized by widespread infection, bacteremia, and relapse, despite standard antibiotic treatment. Because of the difficulty in eradicating salmonella infection in patients with the acquired immunodeficiency syndrome, long-term suppressive treatment with antibiotics seems warranted.

Acquired Immunodeficiency Syndrome↗

Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome.

To examine the cellular immune defect that predisposes patients with the acquired immunodeficiency syndrome (AIDS) to opportunistic infections, we tested T lymphocytes from 16 patients for the capacity to secrete macrophage-activating products (lymphokines) including gamma interferon. Mononuclear cells from 10 of 11 patients did not generate an effective lymphokine in response to mitogen, and 11 of 16 produced subnormal levels of gamma interferon (less than 300 U per milliliter). In addition, upon stimulation with specific microbial antigen, cells from none of 14 patients generated active lymphokines, and cells from 13 to 14 completely failed to secrete gamma interferon. However, the antimicrobial function of monocytes from the patients was intact, and once stimulated with normal lymphokines or gamma interferon alone, macrophages derived from patients' monocytes responded with enhanced and effective intracellular antimicrobial activity. These results suggest that impaired lymphokine production may predispose patients with AIDS to opportunistic infections, and they provide a rationale for using gamma interferon as immunotherapy.

Acquired Immunodeficiency Syndrome↗

Cryptosporidiosis in homosexual men.

Between April 1982 and June 1983, cryptosporidiosis was diagnosed in six homosexual men. Four patients with the acquired immunodeficiency syndrome had lymphopenia, cutaneous anergy, and profoundly impaired cellular immunity; their cryptosporidiosis was severe, unremitting, and refractory to all therapy. Two patients without other opportunistic infections or Kaposi's sarcoma had moderately impaired cellular immunity but not lymphopenia or anergy; their enteric illness was self-limited. Cryptosporidium recently had been recognized as a human pathogen that is transmitted through fecal-oral contamination. The severity of human cryptosporidiosis appears to be determined primarily by immunocompetence of the patient. These six homosexual men, with different degrees of immunologic impairment, had two clinically divergent forms of cryptosporidiosis. Their cases raise questions about human transmission of Cryptosporidium and the prognostic significance of this disease in patients who are at high risk for developing the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Effect of underlying disease and age on pneumococcal serotype distribution.

The hospital records of 264 patients with 277 episodes of pneumococcal bacteremia occurring at New York Hospital-Cornell Medical Center over the period 1970 to 1980 were examined to determine whether serotype distribution varied with the underlying disease or age of the patient. The patients were placed into three groups according to their underlying disease. Group A consisted of all patients with significant impairment of their immune system. Group B included those patients with underlying conditions that were not associated with immune deficiency. Group C comprised those patients considered to be normal hosts. Overall, 84 percent of blood isolates were serotypes included in the vaccine. In Group A, only 73 percent of these isolates were vaccine types, compared with 85 percent in Group B and 97 percent in Group C (differences significant at p less than 0.001). Vaccine serotypes were more common in children than adults (92 versus 81 percent), but in analysis that controlled for underlying disease, the elderly did not differ from younger adults in serotype distribution. The apparent predilection of nonvaccine serotypes to cause bacteremia in immunocompromised patients may be one factor limiting vaccine efficacy in this high-risk population.

Adolescent↗

Phagocytosis and killing of Neisseria gonorrhoeae by Trichomonas vaginalis.

Type 2 and 4 transparent and opaque Neisseria gonorrhoeae demonstrated a logarithmic loss of viability with a half life of approximately 10-30 min when incubated in the presence of Trichomonas vaginalis. Although this effect was observed in the absence of serum for most types of gonococci tested, it was consistently enhanced by the addition of human serum. Only for type 4 transparent gonococci did this process show an absolute serum requirement. Cytochalasin B inhibited the loss of viability. The nonphagocytic cattle parasite Tritrichomonas foetus did not ingest or kill N. gonorrhoeae. Electron microscopy revealed phagocytic uptake and degradation of N. gonorrhoeae in T. vaginalis, indicating that the loss of viability of N. gonorrhoeae was the result of phagocytosis followed by intracellular killing of gonococci by T. vaginalis.

Animals↗