Pediatric patient with accidental theophylline overdose

A 3-year, 10-month female child with a two-year history of asthma developed tachynea, respiratory difficulty and fever. She was accidentally given 750mg of theophylline, an amount 10 times in excess of that prescribed. She became restless, developed tachycardia, and vomited coffee-ground material positive for occult blood. Her serum theophylline level was 67 g ml 1 h and 45 min after being given the drug. She was transferred to the intensive care unit. The hospital immediately referred the...

Oral enzyme artificial cells to deplete other amino acids

The proposal of oral enzyme artificial cells based on the new finding of enterorecirculation of amino acids could also be studied for other genetic enzyme defects. These include the removal of tyrosine in tyrosinemia, histidine in histidinemia, and others. In addition, the basic results obtained here can be useful for analyzing the feasibility for use in other conditions. One example is the use of oral administration of artificial cells containing asparaginase to lower asparagine in leukemia....

Crosslinking of Asparaginase to Polymer Polyethylene Glycol PEG

Peg Asparaginase

The research discussed above showing the use of artificial cells to prevent immunological reactions and to increase the duration of enzyme activity, was based on artificial cells of micron diameter (Chang, 1971a). This is achieved by using interfacial polymerization to form an ultrathin polymer membrane in the form of artificial cells containing enzymes, including asparaginase. A further extension of this method, as discussed in Section 7.5, is to crosslink hemoglobin to asparaginase to form...

PolyHbTyrosinase Artificial Cells for Melanoma Introduction

Melanoma, a fatal skin cancer, is a common tumor which accounts for 10 of all malignancies. The incidence of melanoma has risen dramatically in the last century, doubling every 10 years in many countries. The incidence is now approximately 10 per 100,000 per annum in Europe, giving an approximate lifetime risk of 1 in 200 (Katsambas, Nicolaidou, 1996). Melanoma is most commonly found on the skin, with 10 in the eyes. At least 20 of people diagnosed with melanoma progress to advanced disease and...

Polyhemoglobintyrosinase for melanoma

We therefore introduce a new approach to chemically crosslinking tyrosinase with an excess of hemoglobin to form a soluble polyhemoglobin-tyrosinase (PolyHb-tyrosinase) complex (Figs. 7.1B, 7.7A). This is similar to the PolyHb-asparaginase as described in Section 7.5. PolyHb-tyrosinase carries out two functions 1) Tyrosinase can remove tyrosine needed for growth by melanoma. With a molar Fig. 7.7. (A) Melanoma needs a higher concentration of tyrosine for growth. Similar to PolyHb-asparaginase,...

Enzyme Artificial Cells for Activating Prodrugs Introduction

Pancreatic carcinoma ranks fifth in cancer-related death (Gunzburg and Salmons, 2001). Few of these can be treated surgically, furthermore, radiotherapy and chemotherapy are not effective. Ifosfamide is converted by cytochrome P450 2B1 (CYP2B1) into 4-hydroxyifosfamide that becomes phosphoramide mustard and acrolein that are potentially effective chemotherapeutic agents for Artificial cells containing genetic engineered cells with cytochrome 450 (Lohret al, 2001) phosphoramide mustard &...

Clinical trial results

Lohr et al. (2001) encapsulated human cells transfected with a CYP2B1-expression contruct inside artificial cells to prevent immunorejection (Fig. 7.15). The prodrug, ifosfamide, can diffuse rapidly into the artificial cells to be converted into the active form. They carried out a phase I II study in 14 patients with inoperable pancreatic CA (stages III-IV 86 Stage IV). The typical dose they gave was 250-300 artificial cells (cellulose sulphate membrane) with a mean diameter of 0 8 mm. Each...

Artificial cells containing islets

The largest effort in this area is the use of artificial cells to encapsulate islets for the treatment of diabetes mellitus. As mentioned above, we first put forward the idea of using polymeric cells to encapsulate cells for transplantation (in particular, islet cells) (Chang, 1964,1965,1972 Chang et al., 1966) (Figs. 2.5, 8.1) and thereby to protect them from immune rejection. The author approached the Conaught Laboratories (of insulin fame) to develop his idea of encapsulation of islets for...

First patient on longterm hemoperfusion

This is a 72-year-old female with chronic renal failure and congestive heart failure. She was admitted with complaints of nausea, vomiting, low back pain, diarrhea and hiccups. She was bedridden in the hospital, with a BUN of 186 mg dl,creatinine of 24 mg dl,and a 24 h creatinine excretion of 80 mg. She was placed on peritoneal dialysis but this resulted in massive intra-abdominal bleeding and severeshock. Hemodialysis treatment resulted in hypotension. She was referred to this author since...

Control studies in galactosamineinduced hepatic failure rats

We, therefore, carried out detailed control studies in galactosamine-induced hepatic failure rats to allow for a more valid statistical analysis (Chang etal., 1978 Chang, 1971a, 1978b Chirito etal., 1978, 1979 Mohsini etal., 1980 Tabata and Chang, 1980). With this model we can avoid variations in age, etiology and grades of coma. However, this model may not be the counterpart of fulminant hepatic failure in human. In addition, the survival rate in this model of grade III coma is more like that...

Conjoint Hemoperfusion Hemodialysis

Conjoint Nerve Root

The above results show that hemoperfusion is capable of removing toxin or unwanted waste metabolite and maintain patients symptomfree. On the other hand, the above clinical results also show that hemoperfusion, even with occasional hemodialysis, cannot deal with electrolytes or fluid retention. It has been strongly proposed that middle molecular weight substances, including (3-2-microglobulin (11,800 m.w.), may be responsible for the uremic symptoms. However, the hemodialysis membrane available...