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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 37 records · Page 2Linked to original sources

Intravenous ciprofloxacin for infections in cancer patients.

One hundred forty-seven cancer patients were treated with intravenously administered ciprofloxacin, 200 mg every eight hours, as initial therapy for febrile episodes. Thirty patients (20 percent) were neutropenic (less than 1,000 neutrophils/mm3) at the onset of infection. The overall clinical response rate was 78 percent, 73 percent for neutropenic patients and 79 percent for patients with adequate neutrophil counts. Favorable responses were observed in 19 of 25 patients with bacteremia, 29 of 44 patients with pneumonia, 16 of 18 patients with skin and soft-tissue infection, nine of nine patients with urinary tract infection, 10 of 11 patients with upper respiratory infection, and 26 of 34 patients with fever of undetermined origin. Gram-negative infections were associated with a response rate of 94 percent, gram-positive infections with a response rate of 75 percent, and polymicrobial infections with a response rate of 82 percent. Resistance to ciprofloxacin did not develop and no superinfections were seen. Toxicity was minor except in one patient, in whom a seizure developed. Intravenously administered ciprofloxacin is effective and safe therapy for many infections in cancer patients.

Bacterial Infections

Obstructive manifestations of thyroid lymphoma.

We describe five cases of lymphoma of the thyroid presenting with obstructive symptoms and show some of the associated computed tomographic findings. It is important to consider the diagnosis of thyroid lymphoma when treating patients with obstructive symptoms secondary to an anterior cervical mass, since this disease can be managed nonoperatively.

Aged

Oral ciprofloxacin therapy for infections in cancer patients.

Forty six episodes of infection in 43 cancer patients were treated with oral ciprofloxacin at a dose of 750 mg every 8 h. The overall clinical response was 85%. Patients with microbiologically proven infections had a higher response rate (90%) than patients with infections from whom no causative organism(s) could be isolated (69%). Two of three neutropenic patients responded favourably. Favourable responses were seen in a variety of infections including bacteraemia, urinary tract infection, respiratory tract infection and skin and soft-tissue infection. Resistance to ciprofloxacin developed in one isolate of Pseudomonas aeruginosa. Side effects were mild and were predominantly gastrointestinal in nature. Orally administered ciprofloxacin is safe and effective for the therapy of many serious infections in cancer patients. However, more data are required in patients who are neutropenic.

Adult

New discharge criteria decrease recovery room time after subarachnoid block.

The authors completed a two-phase study to determine criteria that might predict hemodynamic stability during recovery from subarachnoid block (SAB). Patients' supine and sitting (2 min) blood pressures were determined at 30-min intervals in the recovery room (RR). In the first group of 26 patients, retrospective analysis revealed that the orthostatic decrease in mean arterial pressure (MAP) never exceeded 15% following two successive orthostatic decreases of 10% or less. This finding was validated prospectively in a second group of 26 patients. Following two successive orthostatic MAP decreases of 10% or less, none of 65 orthostatic challenges resulted in an MAP decrease of more than 15%; conversely, in the absence of two successive MAP decreases of less than 10%, 5 of 51 orthostatic challenges resulted in an MAP decrease of greater than 15% (P less than 0.02). Had patients been discharged from the RR based on two successive MAP decreases of less than 10%, 35 of 52 patients could have been discharged from the RR 76 +/- 6 min (mean +/- SE) sooner than they would have under usual empirical discharge criteria of supine hemodynamic stability, regression of sensory level to T10, and return of toe movement. Following SAB, hemodynamic stability may return before sensory and motor function; for many patients, orthostatic testing following SAB may safely decrease the amount of time spent in the RR.

Aged

Fetus as an allograft: noncytotoxic maternal antibodies to HLA-linked paternal antigens.

A cellular enzyme-linked immunospecific assay (CELISA) was used to monitor maternal humoral responses in human pregnancy. Non-cytotoxic IgG antibodies to paternal lymphocytes were detected in sera from 6 of 20 normal first trimester primigravidae and 6 of 13 multiparae. No antibody activity against lymphocytes from their partners was detected in sera from any of the 15 nulliparous women. The differences in antibody response between primigravidae and nulliparae (P = 0.024) and between multiparae and nulliparae (P = 0.005) were statistically significant. Lymphocytotoic antibodies to T- and B-lymphocytes were present in sera from three multiparae, but from none of the women in the other two groups. Family studies indicated that the non-cytotoxic pregnancy-associated maternal antibodies were directed to HLA-linked antigens (P less than 0.001). Evidence obtained using cell panels and platelet absorption suggested, however, that these antibodies were not directed to the currently recognized HLA specificities (HLA-A, -B, -C, or -DR).

Enzyme-Linked Immunosorbent Assay

Characterisation of the humoral immune response during murine pregnancy.

Blood samples from female C57BL/10 mice mated with CBA/Ca males were obtained before, during and after both first and second pregnancies. A cellular enzyme-linked immunospecific assay (CELISA) was used to detect maternal antibodies against antigens on paternal splenocytes. Alloantibodies were detected in 48% of mice during or 9 days after a first pregnancy and in 82% of mice by the ninth day after the second pregnancy; these antibodies were first observed on day 10 of the first pregnancy. In two of four active multigravid sera tested, an increase in IgG1 concentration was detected; the level of all other isotypes remained within normal limits. Weak binding of alloantibody to an antigen of approximate molecular weight 44,000 was detected on CBA/Ca splenocytes by immunoblotting sera from multiparous animals. These sera also recognised an antigen of similar molecular weight on H-2b identical 129J splenocytes but not on splenocytes from the maternal strain. These results provide further information on the maternal humoral immune response during murine pregnancy.

Animals

The influence of repeated transfusions and cyclosporine on secondary alloantibody responses in inbred rats.

The influence of cyclosporine (CsA) on secondary and established alloantibody responses was evaluated in inbred Lewis rats and (AO x PVG)F1 hybrid rats. Lewis rats received weekly transfusions of DA whole blood for 8 weeks either with or without cyclosporine (15 mg/kg/day) after sensitization with DA splenocytes. Hybrid rats received only CsA (10 mg/kg/day) after similar sensitization. Administration of CsA did not affect the spontaneous decline in alloantibody titers against class I (RT1A) antigens, but it was associated with a significantly reduced response to class II (RT1B) antigens at the end of the study. CsA prevented maintenance of high alloantibody titers to RT1A antigens in Lewis rats transfused repeatedly following sensitization. IgG alloantibody subclass responses were also altered by CsA with significant reduction in titers of IgG1, 2a, and 2b against RT1A antigens in rats transfused repeatedly; CsA did not, however, suppress IgG2c alloantibody levels in these animals. Responses to public RT1A antigens disappeared in most animals irrespective of their treatment group, whereas those to private and public RT1B antigens persisted unless CsA was administered. The results suggest that, contrary to results obtained with other antigens, CsA does influence secondary alloantibody responses. CsA may thus prove of value in highly sensitized dialysis patients who require further blood transfusions.

Animals

The alloantibody response to semiallogeneic pregnancy in the rat. I. Alloantibodies in sera and placental eluates directed to RT1A antigens.

Maternal alloantibodies to paternal cells were monitored by cellular ELISA, the indirect hemagglutination and erythrocyte antibody rosette inhibition assays in sera and placental eluates from primigravid and multigravid inbred rats. In primigravid animals, antibodies in sera were routinely detected only by the indirect hemagglutination assay and were of low titer; weak antibody activity was detectable only by indirect hemagglutination in 1 of the 8 placental eluates assayed from these animals. Alloantibodies in high titer were present in sera and placental eluates from multigravid rats and were found to be directed predominantly to the RT1A (class I MHC) antigens of the paternal strain. These data provide no support for the hypothesis that the difficulty in detecting maternal antibodies during a 1st pregnancy is due to their preferential binding to antigenic determinants expressed on the placenta.

Animals

The alloantibody response to semiallogeneic pregnancy in the rat. II. Antibodies in serum directed to multiple epitopes on conventional RT1A antigens.

Evidence for a unique class I MHC antigen (termed Pa), which is believed to be expressed on rat trophoblast during pregnancy and which stimulates alloantibody formation with unusual interstrain cross-reactivity, has been examined in inbred rats. The previously reported pattern of crossreactivity was confirmed but was not unique to antisera produced by pregnancy. Antibody blocking studies using biotinylated rat monoclonal antibodies to distinct epitopes on RT1Aa antigens suggested that antibodies present in pregnancy sera, especially from multiparous rats, reacted with several epitopes on these molecules. Moreover, a rat monoclonal antibody, 381- 1E10, directed against the putative Pa epitope was shown by synergistic lysis and cold antibody competition to be directed to the immunodominant S epitope on RT1Aa. These data argue against the existence of a distinct Pa antigen or epitope detected by pregnancy sera.

Animals

Alloantibody and transferable suppressor activity induced by cyclosporine and blood transfusions in the rat.

The effect of cyclosporine on the alloantibody response to blood transfusion was investigated in inbred strains of rats by IHA and CELISA; recipient animals differed from the donors at the class I (RT1A) or both class I and class II (RT1B) antigens of the major histocompatibility complex. Alloantibody titers stimulated in high responder PVGu/c animals by blood transfusions were attenuated by cyclosporine; this effect was not demonstrated in low responder PVGc rats, as alloantibody titers decreased after further blood transfusions whether or not cyclosporine was given. Cyclosporine not only reduced the initial IgM response but suppressed the subsequent production of IgG. Splenocytes from rats receiving cyclosporine and blood transfusions from donors that differed from the recipients at the class I antigen were effective in suppressing the subsequent antibody response to blood transfusion. When blood transfusions from donors which differed from the recipients at both class I and class II antigenic loci were given after splenocyte transfer, a greater degree of immunosuppression was detected than if the transfusion donor differed only at the class I locus. These data suggest that the sensitization produced by blood transfusions and the persistence or decline of the alloantibody response depend upon the responder status of the recipient. Blood transfusions given with cyclosporine are capable of inducing suppressor activity that is transferable in spleen homogenates. Subsequent alloantibody responses are influenced by the class I and class II disparities of the donor and recipient animals. If these results can be extrapolated to clinical practice, cyclosporine should be given with pretransplant blood transfusions to prevent sensitization, and the transfusion donor should differ from the recipient at both class I and class II antigenic loci.

Animals

Human placenta--an antibody sponge?

Maternal IgG antibodies in sera and placenta eluates were studied by a cellular enzyme-linked immunosorbent assay (CELISA) method. Antibodies were not detectable in any of the serum samples obtained before or after delivery from nine normal primigravid women. Antibody activity was, however, present in five of nine placental eluates and two of nine neonatal sera tested in CELISA. Lymphocytotoxic antibodies were not detected in any of the samples tested. These results support the concept that the absence of antibody activity in maternal sera may be caused by the immunosorbent effect of the placenta.

Birth Weight

Unexplained hypotension in Hodgkin's disease.

A 51-year-old black male with progressive polymyositis presented to our hospital with respiratory failure. Hemodynamic monitoring revealed tachycardia, arterial hypotension, a high cardiac index, and low systemic vascular resistance. Evaluation for common etiologies of this hemodynamic pattern was unrewarding. He was found to have Hodgkin's disease of the bone marrow. Aggressive combination chemotherapy led to normalization of heart rate and arterial pressure. It is postulated that Hodgkin's disease through some undetermined mechanism can cause a hyperdynamic circulatory pattern. This hemodynamic state reversed with suppression of the tumor.

Blood Circulation

Antiidiotypic activity in sera from sensitised potential transplant recipients.

Antiidiotypic activity was determined in non-cytotoxic sera from highly sensitised dialysis patients who previously possessed broad-spectrum lymphocytotoxic antibodies. At least four non-cytotoxic sera from six transfused patients were tested in the short antiidiotypic antibody assay against lymphocytes known to be lysed by cytotoxic sera from the same patient. Of 87 sera/cell combinations studied, antiidiotypic activity was detected in 42 (48%). Antiidiotypic activity was present in IgG fractions and F(ab')2 fragments of two active sera. These results indicate that non-cytotoxic sera from patients who were once highly sensitised possess antiidiotypic activity. Fluctuating levels of lymphocytotoxic antibodies frequently encountered in sera from dialysis patients may be explained at least in part by the development of antiidiotypic antibodies.

Adolescent

The influence of cyclosporin A on alloantibody responses in inbred rats: provisional evidence for a serum factor with antiidiotypic activity.

The effect of cyclosporin A (CsA) on alloantibody synthesis has been investigated in inbred F344 (RTl1v1) rats receiving weekly transfusions of DA (RT1a) rat whole blood. Whereas repeated transfusion resulted in a persistent alloantibody response (Group I) administration of CsA (15 mg/kg/day) from either days 0-7 (Group II), days 8-49 (Group III) or days 15-49 (Group IV) resulted in the eventual suppression of alloantibody responses before the end of the experiment on day 49. Antiidiotypic activity was detected in sera obtained on day 49 from animals in Groups II, III and IV, shown to reside in the serum fraction of apparent molecular mass of between 150 and 170 kD and to be specific for alloantisera raised in F344 and the closely related LEW (RTl1) rats but not the unrelated AO (RTlu) strain. These experiments suggest that the immunosuppressive action of CsA may, in part, be due to the development of anti-idiotypic activity whose nature remains to be more fully characterized.

Animals

Viral RNAs synthesized in cells infected with Germiston Bunyavirus.

A rapidly growing strain of Germiston virus was used to study intracellular viral RNA synthesis in BHK cells. The RNAs were separated by electrophoresis into seven bands which fell into three size classes: large (bands L1 and L2), medium (bands M1 and M2), and small (bands S1, S2, and S3). Blot hybridisation established that bands L1, M1, and S1 contained the negative-sense genomic RNAs, while bands L2, M2, S2, and S3 contained positive-sense RNAs complementary to the genomic RNAs within the same size class. After glyoxal treatment the RNAs separated into a large, a medium, and two small bands, indicating that the positive-sense RNAs originally present in bands L2, M2, and S2 are similar in size to their genomic RNAs, while the RNA in S3 is shorter than the small genomic segment. These results suggest that band S2 contains the replicative intermediate RNA and band S3 the messenger RNA of the small genomic segment and also that bands L2 and M2 contain both replicative intermediate and messenger RNAs. Long after virus development had ceased in the infected cells the amounts of RNAs in bands L1, M1, S1, and S2 remained the same, those in bands L2 and M2 were reduced, while only trace amounts of RNAs were observed in band S3, suggesting that the genomic RNAs and the replicative intermediate RNAs form ribonuclease-resistant ribonucleoprotein complexes while the messenger RNAs do not form such complexes. Synthesis of RNA in the infected cells was first evident in bands S3 and M2, after which synthesis was soon observed in all seven bands reaching a maximum rate at the logarithmic phase of growth, suggesting that the pattern of Germiston virus development resembles that of other negative-strand RNA viruses. The presence of defective-interfering particles was indicated by the observation that purified virus preparations contained a minor RNA component originating from the large RNA segment.

Animals

Maternal alloantibody responses during early pregnancy detected by a cellular enzyme-linked immunospecific assay.

Using a cellular enzyme-linked immunospecific assay (CELISA), we have examined sera from nulliparous women and women in the first trimester of a first or subsequent pregnancy for the presence of antibodies directed to surface determinants on peripheral blood lymphocytes from unrelated donors. Maternal antibody activity was found in sera from 1/13 nulliparae, 19/37 primigravidae, and 8/12 multigravidae. Cytotoxic antibody activity was present in 3/12 multigravidae but in no other group. Absorption with packed, pooled platelets did not remove the antibody activity from three of the primigravid sera; unabsorbed sera, however, bound equally well to T and B lymphocytes. These data suggest that the antibody detected by CELISA is not directed to any of the classical HLA antigen series (-A, -B, -C, or -DR) but may be directed to the HLA linked non-class I HT antigen system.

Antigens, Surface

The role of RT1 antigen differences in semi-allogeneic rat pregnancy.

The immunological mechanisms involved in sustaining normal semi-allogeneic pregnancies and in the enhancement of organ allografts were investigated in inbred rats. The antigenic targets for alloantibodies formed after leucocyte transfusions and multiple allogeneic pregnancies were defined by the EA rosette inhibition (EAI) assay in several congenic and recombinant inbred rat strains. Alloantibodies produced by leucocyte immunization (conventionally induced antisera) were directed only to RT1-encoded (major histocompatibility complex, MHC) antigens. Both RT1A (class I MHC) and either RT1B, D (class II MHC) or RT1C (Qa-like) antigens were targets for these alloantibodies; responses to the latter three antigens could not be separated with available congenic recombinant inbred rat strains. Alloantibodies produced as a consequence of multiple semi-allogeneic pregnancies (pregnancy-induced antisera) were directed only to RT1A antigens. Allogeneic pregnancies in which the paternal strain differed from the maternal strain only at the RT1A gene locus produced suppression of a subsequent maternal immune response.

Animals