Prolactin as a tumour marker in cancer of the cervix.

The aim of this study was to determine the possible usefulness of prolactin as a tumour marker in cancer of the cervix. Serum prolactin levels were measured using an enzyme linked immunosorbent assay in 105 women divided into malignant, pre-malignant and control groups. Elevated levels of prolactin were found in 42.9% of patients with malignant disease, 22.9% of controls and 14.2% of individuals with premalignant disease. The differences were not statistically significant. Although prolactin levels were found to be elevated in some patients with malignant disease of the cervix, further studies are needed to establish whether this is of clinical significance.     

Effect of plasma from patients containing bupropion and its metabolites on the uptake of norepinephrine

The uptake of norepinephrine into cortical punches from the brain of the rat was studied in the presence of buffer and plasma from patients containing bupropion and its metabolites. Even though bupropion and its metabolite (compound II) were equipotent in inhibiting the uptake of NE in buffer, compound II was twice as active as bupropion in the presence of human plasma. When the inhibition of uptake of NE in the presence of plasma, obtained from patients on bupropion on steady-state, was correlated with levels of bupropion and its metabolites (II, III, IV) a highly significant correlation was seen in the presence of compound II. Since this compound accumulated in plasma from patients 20-100 times that of the parent compound, the mode of action of bupropion may in part be due to the effect of this compound on the uptake of NE.     

A case of pyrexia from abroad.

A case of pyrexia from abroad presenting to the emergency department is discussed. The causes of such pyrexia are outlined and the investigations are described. We stress that vaccination is not foolproof from acquiring an infection from abroad.     

In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and female B6C3F1 mice to hepatic peroxisome proliferators

The hypothesis that hepatocarcinogenesis resulting from treatmentof rats and mice with peroxisome proliferators is linked toincreased cellular levels of hydrogen peroxide from peroxisomalß-oxidation was investigated. Male F344 rats and femaleB6C3F2₁ mice were treated for 14 days with di(2-ethylhexyl)phthalate(DEHP) or di(2-ethylhexyl)adipate (DEHA), industrial plasticizers,or nafenopin, a hypolipi-demic drug. Activities of enzymes responsiblefor the production [peroxisomal palmitoyl CoA oxidase (PCO)]and degradation [catalase (Cat) and glutathione peroxidase (GSHPx)]of H₂O₂ were assayed in liver homogenates prepared from treatedanimals. The activities of the peroxisomal enzymes PCO and Catwere enhanced 5- to 25-fold and 1.5-to 3-fold respectively bytreatment with the peroxisome proliferators. The activity ofGSHP_x, a cytoplasmk enzyme, was decreased 40–60% in liverhomogenates prepared from treated pnimalx compared to controlanimals. A kinetic treatment of the rates of formation of hydrogenperoxide by PCO, and of degradation of hydrogen peroxide bycatalase was used to estimate steady-state hydrogen peroxideconcentrations ([H₂O₂]) during peroxisomal oxidation of palmitoylCoA. Increases in peroxisomal steady-state [H₂O₂] for the F344rat liver homogenates correlated well with the carcinogenicpotential of these chemicals, determined in previous carcinogenicitystudies. Increases in the steady-state [H₂O2] were also calculatedfor liver homogenates prepared from mice treated with thesecompounds. Decreases in liver lipid peroxidation were observedafter treatment with each chemical in both species. The resultsof these studies are consistent with an involvement of increasedperoxisomal hydrogen peroxide in the hepatocarcinogenesis ofthese compounds.     

In vivo activity of amikacin alone or in combination with clofazimine or rifabutin or both against acute experimental Mycobacterium avium complex infections in beige mice.

The in vivo activity of amikacin, used alone or in combination with rifabutin or clofazimine or both, was assessed in the treatment of early and established Mycobacterium avium complex infections in beige mice. Amikacin given alone at a dose of 50 mg/kg, in one, two, or three divided doses, showed remarkable activity. Addition of clofazimine increased the activity significantly, but addition of the third drug, rifabutin, did not further improve the results. Amikacin-containing regimens are worthy of consideration for investigations in patients with M. avium complex infections.     

Phase I study of liposome-encapsulated c-raf antisense oligodeoxyribonucleotide infusion in combination with radiation therapy in patients with advanced malignancies.

PURPOSE: Raf proteins are key elements of growth-related cellular signaling pathways and are a component of cancer cell resistance to radiation therapy. Antisense oligonucleotides to c-raf-1 permit highly selective inhibition of the gene product and offer a strategy for sensitizing cancer cells to radiation therapy. In this dose escalation study, we evaluated the safety of combined liposomal formulation of raf antisense oligonucleotide (LErafAON) and radiation therapy in patients with advanced malignancies. EXPERIMENTAL DESIGN: Patients with advanced solid tumors were treated with LErafAON in a phase I dose escalation study while receiving palliative radiation therapy. Drug-related and radiation-related toxicities were monitored. Pharmacokinetics and expression of c-raf-1 mRNA and Raf-1 protein were determined in peripheral blood mononuclear cells. RESULTS: Seventeen patients with palliative indications for radiation therapy were entered into this study. Thirteen patients received daily infusions of LErafAON and four received twice-weekly infusions. Radiation therapy was delivered in daily 300-cGy fractions over 2 weeks. Patients tolerated radiation, and no unexpected radiation-related side effects were observed. Drug-related reactions (grade > or =2), such as back pain, chills, dyspnea, fatigue, fever, flushing, and hypertension, were observed in most patients and were managed by premedication with corticosteroids and antihistamines. Serious adverse events occurred in five patients, including acute infusion-related symptoms, abnormal liver function tests, hypoxia, dehydration, diarrhea, esophagitis, fever, hypokalemia, pharyngitis, and tachypnea. Twelve of 17 patients were evaluable for tumor response at completion of treatment; four showed partial response, four showed stable disease, and four experienced progressive disease. The intact rafAON was detected in plasma for 30 minutes to several hours. Six patients with partial response or stable disease were evaluable for c-raf-1 mRNA and/or Raf-1 protein expression. Inhibition of c-raf-1 mRNA was observed in three of five patients. Raf-1 protein was inhibited in four of five patients. CONCLUSION: This is the first report of the combined modality treatment using antisense oligonucleotides with radiation therapy in patients with advanced cancer. A dose of 2.0 mg/kg of LErafAON administered twice weekly is tolerated with premedication and does not enhance radiation toxicity in patients. The observation of dose-dependent, infusion-related reactions has led to further modification of the liposomal composition for use in future clinical trials.