Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.

Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.     

Serial doxycycline and metronidazole in prevention of recurrent periodontitis in high-risk patients.

The efficacy of metronidazole and doxycycline in preventing recurrent periodontitis was studied in 23 patients. After treatment in the previous 7 months with either bimonthly scaling and 3 weeks of systemic doxycycline (11 subjects) or scaling and placebo (12 subjects), patients were monitored for recurrent periodontitis and were scaled every 2 months. When either a periodontal abscess or greater than 2 mm loss of gingival attachment was observed, metronidazole was administered (250 mg every 8 hours) for 10 days. In the placebo plus metronidazole group, 5 patients (42%) exhibited recurrent periodontitis after the metronidazole regimen compared with only one (9%) in the doxycycline plus metronidazole group (P less than 0.096). Subgingival plaque samples at study and healthy control sites were screened for the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum by immunofluorescence and for spirochetes using Ryu's stain. Presence/absence analysis of the sum of scores of the 6 individual pathogens demonstrated large reductions (P less than 0.005) in the frequency of detection of pathogens in the former doxycycline compared with the placebo plus metronidazole group at both study and control sites before and one month after metronidazole. By 7 months after metronidazole, there was no detectable difference between groups. These results indicate that prevention of recurrent periodontitis with metronidazole may be enhanced by previous treatment with doxycycline.     

Fulminant childhood hemophagocytic syndrome mimicking histiocytic medullary reticulosis. An atypical form of Epstein-Barr virus infection.

Ten cases of pediatric fulminant hemophagocytic syndrome, encountered between 1986 and 1989, are described. They occurred in the summer, and the patients presented with fever, jaundice, hepatosplenomegaly, pancytopenia, coagulopathy, and abnormal liver function. Bone marrow studies revealed infiltration by atypical T-lymphoid cells, rare B immunoblasts, and mature histiocytes with hemophagocytosis. Initially, histiocytic medullary reticulosis was suspected in six cases. The clinical course was characterized by rapid deterioration, with a mean period of 16 days from onset of fever to death. The main causes of death were coagulopathy with multiple organ failure and opportunistic infection. In seven of eight cases studied by serologic assay and Southern blot hybridization, acute or active Epstein-Barr virus (EBV) infection was documented. It is suggested that an atypical or fulminant form of primary EBV infection distinct from classic infectious mononucleosis was prevalent in previously healthy children in Taiwan. Younger age involvement and seasonal clustering were characteristic of the disorder described.     

Kupffer cell modulation of the systemic immune response

The effects of global hepatic injury and of Kupffer cell activation on systemic immunity were studied in an in vivo rat model, using the diameters of the delayed-type hypersensitivity (DTH) response to keyhole limpet hemocyanin and of a subcutaneous Staphylococcus aureus abscess as measures of systemic immunoresponsiveness. Hepatic injury with carbon tetrachloride resulted in significant suppression of the DTH score (5.5 +/- 0.7 vs 8.8 +/- 0.8 mm). Kupffer cell activation with intraportal Escherichia coli was likewise suppressive (DTH score, 4.4 +/- 0.5 vs 6.1 +/- 0.4 mm for animals receiving systemic E coli); the magnitude of this suppression correlated with the numbers of organisms extracted by the liver. Conversely, Kupffer cell ablation with carrageenan lessened the immunosuppressive effects of anesthesia and surgery (DTH score, 8.5 +/- 0.9 vs 6.8 +/- 0.6 mm for controls; S aureus abscess, 4.1 +/- 0.4 vs 5.7 +/- 0.4 mm for controls). These results indicate that Kupffer cells can modulate the systemic immune response and suggest that gram-negative portal bacteremia with resultant Kupffer cell activation may contribute to the immunologic derangements characteristic of trauma and critical surgical illness.     

Effect of changing medication regimens in glaucoma patients

When glaucoma medication fails to adequately control intraocular pressure (IOP), a second medication is frequently added. Before adding a second drug to patients whose IOP was no longer controlled by 0.5% timolol, we tested the effect of switching to another beta blocker, levobunolol (0.5 or 1%). We also evaluated the effect of study participation on compliance in the control group continuing to receive 0.5% timolol. In each treatment group, the IOP of approximately 30-40% of the patients was successfully controlled for the 3-month study period. The remaining patients did not exhibit significant pressure reductions and were dropped from the study within 2 weeks. We concluded that (1) the results of 'switch' studies without a control group must be interpreted carefully, and (2) the initiation of a 'new regimen' with an equieffective beta blocker may be sufficient to increase compliance and thereby control IOP.     

Clinical uses of intravenous immunoglobulins

Immunoglobulins are an important component of host defense against infections. They also play a central role in immune regulation. A wide spectrum of human diseases is associated with decreased or abnormal regulation of immunoglobulin levels. Recently IV preparations of immunoglobulin have become available for clinical studies. There are already substantial data indicating a useful role for IV immunoglobulin in patients with primary hypogammaglobulinemia, neonates predisposed to group B streptococcal infections, individuals with ITP, children with Kawasaki disease, and bone marrow transplant patients predisposed to CMV infections. Promising data have been reported in burn patients and in individuals with CLL; these data require confirmation. Potential areas for future investigation include AIDS, autoimmune disorders, and viral disorders other than CMV.