TREATMENT OF MALIGNANCY-ASSOCIATED HYPERCALCEMIA WITH NORETHISTERONE: A CASE REPORT

Hypercalcemia is a common cause of morbidity in cancer patients. The mechanism of malignancy-associated hypercalcemia includes increased bone resorption and decreased renal calcium clearance which also occur in primary hyperparathyroidism. Norethisterone can inhibit bone resorption and has recently been shown to be effective treatment for mild hyperparathyroidism in post menopausal women. We report the successful use for the first time of norethisterone (5 mg daily) in a case of malignancy-associated hypercalcemia after other standard agents failed. (Aust NZ J Med 1989; 19: 51–54.)     

Metachronous cancer: Prognostic factors including prior irradiation

In this article we evaluate two factors that may be responsible for the reported increased mortality rate in metachronous cancers: prior radiation therapy and stage at presentation. A select group of 358 patients was split into three groups: no prior cancer (group 1), prior cancer treated with radiation therapy (group 2), and prior cancer treated with surgery alone (group 3). We compared survival among the three groups according to stage (T1 or T2 vs. T3 or T4) using the Lifetest procedure. Survival in patients with advanced (T3 or T4) cancers was uniformly poor, and survival in patients with low-staged (T1 or T2) cancers was disproportionately poor only for patients in group 2. Metachronous cancers are not necessarily more lethal, except when the cancer arises within prior irradiated tissue. Initial treatment decisions for patients with primary cancers must always provide for the contingency of a metachronous cancer, and the judicious use of radiation therapy is essential. (Otolaryngol Head Neck Surg 1998;119:619-23.)     

In-vitro permeation of some β-blockers across the hairless mouse skin

Abstract— To support the development of a suitable transdermal dosage form for β-blockers, in-vitro, skin permeation studies of nine β-blockers were conducted at 37°C across the excised abdominal skin of hairless mouse mounted on the receptor compartment of a two-chambered Valia-Chien glass diffusion cell. The drugs varied in lipophilicity, whereas pK_a values were comparable. Permeability coefficients were calculated from the steady-state flux values. Agreement was found between the permeability coefficient and the drug lipophilicity, expressed as the octanol-bufter distribution coefficient.     

Management of Patients with Supra ventricular Tachycardia Using Amiodarone Therapy

Amiodarone has emerged as a potent agent for the management of patietits with reentrant supra ventricular tachycardias, atrial flutter, atrial fibrillation, and dysrhythmias associated with the preexcitation syndromes. Efficacy is reported betiveen 50 and 90% dependent upon the nature of the primary rhythm disturbance and population studied. Electrophysiological studies have not in general been helpful in predicting outcome with this agent. The drug may produce a wide array of toxic side effects, requiring cessation of therapy in less than 10% of patients. Our approach to the use of this agent relegates it to a second or third line of therapy in view of its complex pharmacokinetics and wide array of side effects.     

Myocardial Protection

Early studies of myocardial protection were designed to minimize ischemic injury. The next class and generation of investigations will most likely be designed to accelerate recovery following known myocardial injury. Such techniques will play an important role in allowing operations on acutely injured and ischemic myocardium and will be important in the treatment of postischemic injury when such injury occurs during the course of complex cardiac operations. Surgical aspects of myocardial metabolism are still rudimentary and many empiric observations require further exploration into the mechanisms by which such applications work.     

Interrelationship of Rheumatoid Arthritis, Folic Acid, and Aspirin

Decreased serum folate (FA) levels weredetected in 71% of 51 patients withrheumatoid arthritis (RA). Of 11 patientsstudied more intensively, only one fulfilled the usual hematologic criteria forFA deficiency. All, however, demonstrated an abnormally rapid plasmaclearance of tritium-labeled pteroylglutamic acid (³HPGA). "Binding" of³HPGA was evaluated by dialysis to apparent equilibrium and found to be significantly reduced in the sera of patientswith RA. Common to all these patientswas the ingestion of aspirin (ASA). FourRA patients not taking ASA had normal³HPGA "binding". The ³HPGA "binding"of RA sera decreased as these patientswere given increased ASA dosage andvice versa. The in vitro addition of ASAto normal sera reduced "binding" to thelevel detected in RA sera. Progressiveincreases in ASA resulted in progressivedecreases in "binding". Aspirin given tothree normal subjects reduced ³HPGA"binding" in all and serum FA in two.Precedents for ASA-induced structuralchange in binding proteins and for therelation between decreased binding andlowered serum levels are discussed. It issuggested that the low serum FA concentration and rapid plasma clearanceof ³HPGA in RA might reflect ASA-induced alterations of FA binding, resulting in a redistribution rather thandeficiency of this vitamin.

Submitted on February 16, 1971 Revised on May 6, 1971 Accepted on May 10, 1971     

The Effectiveness of Combinations of Antileukemic Agents in Inducing and Maintaining Remission in Children with Acute Leukemia

1. Combinations of effective agents produce at least an additive increase in complete remission rates over that which can be achieved when the agents are used individually.

2. Patients who do not achieve complete remission with initial treatment have a significantly shorter survival.

3. Alternating MTX and 6-MP at 28-day intervals during remission does not prolong the duration of remission over that of combined concurrent 6-MP and MTX.

4. The administration of folic acid antagonists intrathecally at 28-day intervals during antimetabolite maintained remission did not prolong the duration of remission. Meningeal leukemia, however, occurred significantly less frequently in these patients.

5. The duration of combined 6-MP and MTX maintained remission is not greater than that of 6-MP maintained remission.

6. The toxicity of 6-MP and MTX in combination in patients in remission is additive.

The above conclusions were drawn from this comparative study of combinations of chemotherapeutic agents in children with acute lymphocytic leukemia.

Submitted on September 11, 1964 Accepted on February 23, 1965