PubMed · 4139656
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J F Mackin, J J Canary, C S Pittman. 1974-12-26. Thyroid storm and its management.. https://doi.org/10.1056/nejm197412262912607
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In a new guideline issued by the German Association for the Study of Pain, intrathecal opioid therapy is described as proven to be effective with relatively few side effects. We reviewed this statement by analysis of the available literature and critical evaluation of the clinical course in a few of our own patients (n=3). In these cases (as well as in a further eight patients), explantation and a switch to oral opioids led to distinctly better alleviation of pain and abatement of the unwanted effects. The problems we discuss do not appear to be rare instances, but by all means complications that are frequently described. The long-term efficacy of intrathecal opioids has not been adequately verified; moreover, their potency is not high. The frequency of undesired events is comparable to that of oral opioid medication, but serious neurological complications are possible. To avoid dose escalations and to recognize neurological complications in time, diligent monitoring by the surgeon or an experienced pain center is essential.
AIM: To compare the performance of oral fundus fluorescein angiography with a confocal scanning laser ophthalmoscope (SLO) with intravenous fundus fluorescein angiography (IVFFA) with a fundus camera in the assessment of sight-threatening diabetic retinopathy. PATIENTS AND METHODS: A total of 25 patients undergoing IVFFA to investigate their diabetic retinopathy were recruited. Participants returned 1 week later and an oral angiogram with the SLO was performed. Six facets of the oral and intravenous angiograms were scored and compared: visualization of the foveal avascular zone (FAZ); branch retinal identification; macular leakage; identification of microaneurysms in areas of macular leakage; peripheral nonperfusion, and leakage from neovascular complexes. RESULTS: Compared to IVFFA, the FAZ was unreliably visualized with oral angiography (Kappa 0.1, 95% CI 0-0.3). In contrast, macular leakage (Kappa 0.78, 95%, CI 0.72-0.83), identification of microaneurysms in areas of macular leakage (Kappa 0.78, 95%, CI 0.72-0.83), and neovascular complexes (Kappa 1.0) were reliably seen. Analysis of the visualization of peripheral nonperfusion was complicated by the finding that profuse dye leakage from neovascular complexes obscured the view of the peripheral retina. If the five angiograms in which this occurred were excluded, oral angiography identified 23 of the 24 eyes in which significant nonperfusion was found on IVFFA. CONCLUSION: Oral angiography with the SLO can provide high-quality angiograms that allow judgments to be made about the presence of treatable diabetic maculopathy, proliferative diabetic retinopathy, and peripheral nonperfusion. In the presence of coexisting macular oedema, it proved to be an unreliable technique with which to investigate foveal ischaemia.
In this work, we investigated the anticancer activity of orally administered recombinant human lactoferrin (rhLF) alone and in combination with chemotherapy in tumor-bearing mice. rhLF inhibited the growth of squamous cell carcinoma (O12) tumors in T cell-immunocompromised nu/nu mice by 80% when administered at 1,000 mg/kg (2.9 g/m2) by oral gavage twice daily for 8 days (p < 0.001). Similar activity was observed in syngeneic, immunocompetent BALB/c mice, where orally administered rhLF (1,000 mg/kg, 2.9 g/m2 once daily) halted the growth of mammary adenocarcinoma TUBO. Oral rhLF (200 mg/kg, 0.57 g/m2) was also used alone and in combination with cis-platinum (5 mg/kg) to treat head-and-neck squamous cell carcinoma in a syngeneic murine model. Monotherapy with oral rhLF or cis-platinum caused 61% or 66% tumor growth inhibition over placebo, respectively. Mice receiving both therapies showed 79% growth inhibition, a statistically significant improvement over each drug alone. We then demonstrated that administration of oral rhLF (300 mg/kg, 0.86 g/m2) to tumor-bearing or naive mice resulted in (i) significantly increased production of IL-18 in the intestinal tract, (ii) systemic NK cell activation and (iii) circulating CD8+ T-cell expansion. These data suggest that oral rhLF is an immunomodulatory agent active against cancer as a single agent and in combination chemotherapy, exerting its systemic effect through stimulation of IL-18 and other cytokines in the gut enterocytes. rhLF has been administered orally to 211 people without a single serious drug-related adverse event. Thus, rhLF shows promise as a safe and well-tolerated novel immunomodulatory anticancer agent.