Derek F. Stubbs

Methylprednisolone as an Intervention Following Myocardial Infarction

: Eight hundred and forty-two patients undergoing treatment for rheumatoid arthritis in hospital centres in the United Kingdom were evaluated as part of a long-term, variable dose study of the efficacy and safety of flurbiprofen in 1,396 patients with a variety of rheumatological disorders. Highly significant (p less than 0.001) improvements were evident in morning stiffness, grip strength, joint size, articular index and functional capacity at the end of the 18-month observation period reported here, as was a decrease in pain severity in all sub-groups, including those patients entering the study because of lack of effect of their previous therapy. Global assessments by doctor and patient showed highly significant improvements over this time period for both young and older patients, in whom objective improvements were less striking. Sixty-four per cent of side-effects reported were gastro-intestinal, CNS side-effects (headache, giddiness) accounting for 14%. The incidence varied according to whether or not concomitant therapy was being prescribed. Side-effects in the elderly were similar in nature to those in younger patients.

Double-Blind Placebo-Controlled Efficacy Study of Ketazolam (U-28,774)

The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46.9 mg administered as a once-a-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physicians Global Impressions, two Patients Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKGs, laboratory tests, or physical examinations.

Post-Acute Myocardial Infarction Symptomatic Pericarditis (PAMISP): Report on a Large Series and the Effect of Methylprednisolone Therapy

One thousand one hundred and fifty-eight patients sustained a presumed myocardial infarction. Ninety-six per cent of the cases were complicated by ventricular failure. Five hundred and eighty-nine patients were randomized to receive methylprednisolone sodium succinate (MPSS, Solu-Medrol(R)Sterile Powder, The Upjohn Company) (two doses of 2 to 3 g i.v. three hours apart within 12 hours of the onset of chest pain) and 569 to placebo. 7.5% of patients receiving MPSS and 18.5% of the patients on placebo had post-acute myocardial infarction symptomatic pericarditis (PAMISP) (p < 0.001). The MPSS-treated patients needed less therapy for their PAMISP, and MPSS pre-treatment attenuated and limited the PAMISP. Patients who suffered PAMISP did not differ in age or sex from patients without PAMISP, but had a 3-4-fold greater incidence of anterior acute myocardial infarctions (AMIs). The literature is also reviewed to show that MPSS is a beneficial intervention in PAMISP and other pericarditides.

Frequency and the brain.

Abstract The brain is an information handling device. The information is coded as the frequency of nerve action potentials. Mechanisms of the encoding and manipulation of information are discussed. A general discussion of the cortex as a frequency generating and frequency sensitive device is given.

Positive Synergism between Diuretics and Methylprednisolone Following Acute Myocardial Infarction

In studies of patients with cardiac failure following an acute myocardial infarction, 1114 patients were followed for 7-day mortality. In the 45% of patients receiving diuretics on day 1, the death rate was twice that of patients not receiving diuretics. In patients treated 6 to 12 hours following the onset of chest pain, mortality was 2.8 times that of patients treated within 6 hours of the onset of chest pain. Randomization to methylprednisolone sodium succinate (MPSS, Solu-Medrol(R)Sterile Powder, The Upjohn Company) did not improve the low mortality rates of those patients who did not need diuretics nor who were treated early. However, patients who were treated late and who needed diuretics and who were randomized to MPSS had a death rate half that of those who received placebo.

Significance of Infarct Site and Methylprednisolone on Survival Following Acute Myocardial Infarction

Eight hundred and forty-nine patients with confirmed myocardial infarction were enrolled in a double-blind, placebo-controlled clinical trial of the efficacy of methylprednisolone sodium succinate (MPSS, Solu-Medrol(R) Sterile Powder, The Upjohn Company) for reduction of morbidity and mortality following an acute myocardial infarction complicated by left ventricular failure. Two study groups were prospectively defined based on time from onset of chest pain to administration of investigational therapy. Study Group 1 received investigational therapy before 6 hours had elapsed while Study Group 2 was treated 6 to 12 hours from the onset of chest pain. Both study groups were randomized to receive either a 30 mg/kg i.v. dose of MPSS (3 g maximum) or a matching placebo at the time of study admission, to be followed by an identical dose three hours later. Definitive electrocardiograms were available for 814 patients at admission. The mortality rates at 28 days and 6 months for the anterior transmural and nontransmural infarctions did not differ significantly with regard to time to treatment or investigational therapy. For the inferior/posterior transmural infarctions, however, there was a 92% relative reduction in mortality at 28 days in the MPSS treatment arm of Study Group 2 (1/83 [1.2%] for patients given MPSS versus 15/97 [15.5%] for those given placebo; p<0.001). This significant difference persisted at the 6 month follow-up evaluation (3/82 [3.6%] for patients on MPSS versus 17/96 [16.6%] for those on placebo, P < 0.01). Site-specific efficacy has been reported for the anterior infarction groups of the major beta-blocker trials. The mechanism of action for the differential effect in these trials, as with the MPSS trial reported here, remains to be determined

Simple prediction of 28-day mortality following an acute myocardial infarction.

Upon admission to a drug study of 1,122 patients with myocardial infarction, twenty-seven questions relating to the patients’ cardiac status were answered by the physicians. These questions were categorized into four groups of related items of signs and symptoms. Thus four scores could be completed: degree of infarction score, cardiogenic shock score, cardiac failure score, and overall-state-of-the-patient score. The scores were all found to be highly correlated with 28-day mortality. Also, since these scores can be easily and immediately determined at the bedside, or with standard tests, they are both convenient and accurate predictors of 28-day mortality following a myocardial infarction.

Physician-Patient Communication: Agreement between Them

15 patients with chronic anxiety completed a questionnaire before and after therapy and the physician independently completed the questionnaire on each patient. The responses of patients and physician for each patient and question were compared by examining means, a concordance matrix, and Cohens weighted kappa. It was concluded that agreement is greatest: (1) after therapy, (2) when relative change during therapy is greater, (3) when the average level of symptomatology expressed by the patient is nil or severe. Examination of means alone or individual questions permitted no conclusions.