Preliminary report: imaging of Kaposi sarcoma and lymphoma in AIDS with indium-111-labelled liposomes.

Kaposi sarcoma and malignant lymphoma were successfully imaged with high purity liposomes containing indium-111 in two patients with AIDS. Gamma camera images of the patient with Kaposi sarcoma showed four discrete lesions along the left foot and calf with no foci along the right foot, and no uptake into clinically enlarged but non-neoplastic lymph nodes. The spread of the Kaposi sarcoma was proximal along the leg. The neoplastic cervical lymph nodes in the second patient who had large-cell diffuse intermediate grade lymphoma were also imaged successfully. Since Kaposi sarcoma and lymphoma frequently involve occult sites, liposome imaging may prove useful in the diagnosis and management of these diseases.

Clinical safety and tolerance of mitoxantrone.

Mitoxantrone has been administered to more than 4000 patients worldwide. From this data base, a summary of the latest information is presented on the effect of mitoxantrone on bone marrow, on its nonmyelosuppressive acute toxicities, on its local tolerability, and on measurements of organ function. Most of these patients had solid tumors and were treated with an initial dose of mitoxantrone (12 to 14 mg/m2). Predictable leucopenia was dose limiting, but clinically significant suppression of RBC or platelet count was rare. Other hematologic or blood chemistry abnormalities were infrequent. The most common adverse clinical effects were nausea and vomiting, stomatitis, and alopecia, though the majority of these cases were mild. Many patients experienced no adverse reactions to mitoxantrone; there have been no reports of cellulitis, vesication, or tissue necrosis following extravasation. From the global experience with mitoxantrone, it seems that for patients who have not previously received anthracycline therapy, the risk of congestive heart failure is minimal up to a cumulative mitoxantrone dose of 160 mg/m2. In randomized, comparative clinical trials in advanced breast cancer, using mitoxantrone or doxorubicin either as single agents or in combination with other standard drugs, the incidence of moderate or severe acute toxic side effects was much lower for patients treated with mitoxantrone or mitoxantrone-containing combinations. From these data, it is clear that mitoxantrone has an exceptional safety profile, particularly with regard to acute nonmyelosuppressive toxicity and local tolerability. This offers the patient a better quality of life during antineoplastic chemotherapy.

Side effect and safety data for fenbufen.

The overall safety pattern of fenbufen has been evaluated in a total of 2,667 patients: 1,667 of them in domestic clinical studies and 1,000 in foreign pivotal studies. Comparisons of several hundred patients--each receiving aspirin, indomethacin, and placebo--were made. Detailed analysis of all reported adverse effects demonstrated that fenbufen is a relatively safe nonsteroidal anti-inflammatory drug. The incidence and severity of adverse gastrointestinal experiences in patients treated with fenbufen were less than those in patients treated with either aspirin or indomethacin. Life-table analysis showed that during the first three months of therapy, the overall incidence and severity of gastrointestinal reactions due to fenbufen therapy were similar to those observed with placebo therapy. Cutaneous disorders were reported in more fenbufen- than placebo-treated patients during the first month of therapy, thereafter, the incidence was the same. Clinical laboratory results were evaluated in the 1,667 patients who received fenbufen in domestic studies. Elevations of alkaline phosphatase and serum glutamic oxaloacetic transaminase levels, occurred occasionally with eosinophilia, particularly during the first four weeks of therapy with fenbufen. In the majority of cases, however, these abnormal values returned to normal or near-normal values with continuance of fenbufen therapy. No cases of drug-related jaundice have been reported either in clinical trials or from countries where fenbufen is marketed. No clinically significant changes were observed in other laboratory parameters including total bilirubin, blood urea nitrogen, white blood cell count, platelets, hematocrit, hemoglobin, and stool occult blood. In summary, fenbufen was well tolerated and provides a good therapeutic ratio, particularly in respect to gastrointestinal intolerance.

Project planning, investigator selection, data harmonization.

This paper has presented certain concepts and thoughts regarding the planning process and dealt with two areas where planning and preconsideration of problems will aid in the quality, speed and efficiency of ones programs. The varied examples that have been cited are just that; they are not intended to be a comprehensive evaluation of all the aspects of the planning process or, for that matter, the selection of investigators or harmonization of data. They are intended instead to illustrate the way in which a comprehensive and thorough planning approach to project management can facilitate, ease and improve the quality of the work we do. The important point of this whole paper is not so much the individual benefits to be gained from any one of the systems described, but rather to illustrate as much as possible the value of planning in our process. It is incumbent on us to search for ways to improve the way in which we do or work. Standards have improved considerably over the years, but there is much room for further improvement; good clinical and scientific thought will inevitably continue to contribute to the improvement of those programs. The submission of this author, however, is that if we do these in advance, we will solve them a good deal faster and a good deal more efficiently than if we constantly react to new and developing problems.

Cimetidine, antacid, and hospitalization in the treatment of benign gastric ulcer: a multicenter double blind study.

Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.

Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial.

The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.

The interrelation of thermoregulatory and baroreceptor reflexes in the control of the blood vessels in the human forearm.

1. The interrelation of thermoregulatory and baroreceptor reflexes in the control of the circulation through the forearm has been investigated in eight men.2. The results are compatible with the current hypotheses that thermoregulatory reflexes employ exclusively blood vessels in the skin, and that baroreceptor vasodilator reflexes excited by transfer of blood from the legs to the trunk employ exclusively blood vessels in the muscles. They are compatible with the hypothesis that baroreceptor vasoconstrictor reflexes excited by transfer of blood from the trunk to the legs employ blood vessels in muscles, but not with the hypothesis that they do so exclusively.3. The results indicate that when blood is transferred from the trunk to the legs, vasoconstriction over-rides thermoregulatory vasodilatation, presumably in the blood vessels of the skin.4. The circulation through the skin appears, therefore, to be under baroreceptor as well as thermoregulatory reflex control, and over the short period of time examined, namely 1 min, the baroreceptor control takes precedence.