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toms that are being observed with increasing frequency This toxic manifestation appears to be related to the total amount of drug administered, and it usually improves slowly after it has been discontinued Biopsies of peripheral nerve have shown a primary axonal degeneration Approximately one-third of patients receiving this drug also experience tinnitus or high-frequency hearing loss or both Otoxicity is also dose-related, cumulative, and only occasionally reversible Some protective effect has been claimed with the use of the melanocortin compound ACTH (4-9), but the bene ts in a trial by Gerristen and colleagues were quite small and probably do not justify its administration on a routine basis Retrobulbar neuritis occurs rarely Seizures associated with drug-induced hyponatremia and hypomagnesemia have been reported

Taxol (paclitaxel) and Taxotere (docetaxel) are newer anticancer drugs derived from the bark of the western yew Both are particularly useful in the treatment of ovarian and breast cancer, but they have a wide range of antineoplastic activities A purely or predominantly sensory neuropathy is a common complication These drugs are thought to cause neuropathy by their action as inhibitors of the depolymerization of tubulin, thereby promoting excessive microtubule assembly within the axon The neuropathy is dose-dependent, occurring with doses greater than 200 mg/m2 of paclitaxel and at a wide range of dose levels for docetaxel (generally over

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This enzymatic inhibitor of protein synthesis is used in the treatment of acute lymphoblastic leukemia Drowsiness, confusion, delirium, stupor, coma, and diffuse EEG slowing are the common neurologic effects and are dose-related and cumulative They may occur within a day of onset of treatment and clear quickly when the drug is withdrawn, or they may be delayed in onset, in which case they persist for several weeks These abnormalities are at least in part attributable to the systemic metabolic derangements induced by L-asparaginase, including liver dysfunction In recent years, increasing attention has been drawn to cerebrovascular complications of L-asparaginase therapy, including ischemic and hemorrhagic infarction and cerebral venous and dural sinus thrombosis Fineberg and Swenson have analyzed the clinical

features of 38 such cases These cerebrovascular complications are attributable to transient de ciencies in plasma proteins that are important in coagulation and brinolysis

This is a pyrimidine analogue, used mainly as a secondary treatment of cancer of the breast, ovary, and gastrointestinal tract A small proportion of patients receiving this drug develop dizziness, cerebellar ataxia of the trunk and the extremities, dysarthria, and nystagmus symptoms that are much the same as those produced by cytarabine (Ara-C; see below) These abnormalities must be distinguished from metastatic involvement of the cerebellum and paraneoplastic cerebellar degeneration The drug effects are usually mild and subside within 1 to 6 weeks after discontinuation of therapy The basis of this cerebellar syndrome is not known

machines speak the same language The modern Internet is such that you can use any type of computer IBM-compatible, Mac, or other and take advantage of all the network s resources All Internet activity consists of computers talking to one another This occurs in machine language However, the situation is vastly more complicated than when data goes from one place to another within a single computer In the Internet (often called simply the Net), data must often go through several different computers to get from the transmitting or source computer to the receiving or destination computer These intermediate computers are called nodes, servers, hosts, or Internet service providers (ISPs) Millions of people are simultaneously using the Net; the most efficient route between a given source and destination can change from moment to moment The Net is set up in such a way that signals always try to follow the most efficient route If you are connected to a distant computer, say a machine at the National Hurricane Center, the requests you make of it and the data it sends you, are broken into small units called packets Each packet coming to you has, in effect, your computer s name written on it But not all packets necessarily travel the same route through the network Ultimately, all the packets are reassembled into the data you want, say, the infrared satellite image of a hurricane, even though they might not arrive in the same order they were sent Figure 33-5 is a simplified drawing of Internet data transfer for a hypothetical file containing five packets transferred during a period of extremely heavy usage Nodes are shown as black dots surrounded by circles In this example, some packets pass through more nodes, and/or over a much greater physical distance, than others If Net traffic were very light, all the packets might follow the same route through fewer nodes This is why it takes longer to acquire data on the Net during peak hours of use, as compared with times when there are comparatively few people connected into it A file.

given in conventional intravenous doses, but intracarotid injection of the drugs may cause orbital, eye, and neck pain, focal seizures, confusion, and possibly focal neurologic de cits Postmortem examinations of patients who had been treated with intravascular BCNU have disclosed a diffuse vasculopathy characterized by brinoid necrosis and microthrombi and diffuse foci of swollen axis cylinders and myelin vacuolization (Burger et al, Kleinschmidt-de Masters)

Cytarabine (Ara-C)

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