The Effect of Cross-Linking on the In Vivo Disintegration of Hard Gelatin Capsules

Purpose. To evaluate if the cross-linking of gelatin affects in vivo capsule disintegration. Methods. Scintigraphic investigation in nine healthy volunteers to provide for a real time visualisation of capsule disintegration. Results. The moderately stressed capsules failed the USP dissolution specification for acetaminophen capsule when tested in water and conventional SGF but passed with the addition of pepsin. Moderately stressed capsules started to disintegrate at 10 ± 6 minutes (range 6 to 24 minutes) compared to 8 ± 2 minutes (range 5 to 11 minutes) for the unstressed capsule. Conclusions. The results of the study clearly demonstrate that with the incisive technique of gamma scintigraphy there are no differences in the in vivodisintegration properties of moderately stressed and unstressed capsules.     

X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features

The radiologic studies of 38 essentially untreated adults with X-linked hypophosphatemia (XLH) were reviewed to determine the prevalence of radiologic features, to compare the findings in men and in women, and to elucidate the natural history of the disease by comparing the findings in young, intermediate-age, and older patients. Bone-reinforcement lines were common, but no characteristic mineral mass alteration was established. Looser zones were more prevalent in older subjects. Osteoarthritis was common, occurring in the ankles, knees, feet, sacroiliac joints, and wrists. Enthesopathy was infrequent in the younger group but was present in every member of the intermediate and older groups and was often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Three new skeletal alterations in XLH were found to be common: flaring of the iliac wings, trapezoidal distal femoral condyles, and alterations in talar morphology, including shortening of the talar neck and flattening of the talar dome. Technetium-99m methylene diphosphonate scintigrams of 17 subjects were often abnormal, depicting bowing deformity and focal tracer accumulation in diaphyseal cortices and in periarticular and extraarticular regions. The mean metabolic index was moderately elevated (4.0). Both radiographic and scintigraphic findings were more severe in men, consistent with hemizygosity. The natural history of untreated XLH in both sexes is characterized by the development of a variety of age-related skeletal abnormalities during adulthood.     

Phase II trial of oral piritrexim in advanced, previously treated transitional cell cancer of bladder

Oral piritrexim (PTX), a second generation antimetabolite, has been shown to be an active agent against methotrexate refractory transitional cell cancer (TCC) of the bladder in phase I trials. We conducted a phase II trial of this drug in patients with TCC of the bladder who failed a first line chemotherapy regimen.Methods: Oral PTX was started at the dose of 25 mg three times per day for 5 days weekly for 3 weeks followed by one week of rest. If this was tolerated the dose was increased to 50 mg three times a day. Patients were monitored for response rate and toxicity.Results: Seventeen patients were entered into the trial. Two patients did not complete the required 2 courses of treatment to be evaluable. There were 13 evaluable patients. Among the 13 no one achieved a complete response (CR), however, there were 3 partial responses (PRs=RR: 23%) and 5 stable diseases (SDs). The responses lasted 2, 8 and 14 months. The major dose limiting toxicity was myelosuppression. Two patients died on treatment. One death was due to neutropenic fever and the cause of death in the second patient is thought to be a cerebral vascular accident (CVA).Conclusion: PTX is an active drug in the treatment of TCC of the bladder. Bone marrow suppression is the most common dose limiting toxicity. In view of the observed responses and toxicities in this study and other studies, we suggest that the role of PTX be further investigated in the following clinical settings:1. Palliative initial treatment in patients with TCC of bladder who are not candidates for more aggressive chemotherapy.2. As first line chemotherapy in combination with other active drugs.     

Clinical use of intravenous phenytoin sodium infusions

The safety of administering phenytoin sodium by intermittent intravenous infusion was evaluated. Twenty-eight adult patients in a neurosurgical intensive-care unit were studied; most patients had head trauma. Ninety-three doses of phenytoin sodium 300 mg in 0.9% sodium chloride injection 50 ml were administered according to hospital-approved guidelines, which included administration over 30-60 minutes, initiation of infusion within one hour of solution preparation, and use of a 5-microns inline filter. All patients were monitored for adverse reactions and were on continuous ECG monitoring. Analysis of clinical data before and immediately after phenytoin infusions showed no statistically significant change in blood pressure and a small but significant drop in mean heart rate. There were no cases of hypotension, arrhythmias, bradycardia, or phlebitis. Single occurrences of hypertension, nystagmus, and pain at the i.v. site were noted. It is concluded that careful infusion of phenytoin sodium in 0.9% sodium chloride injection is safe. The use of approved written guidelines to govern important factors of preparation and administration are recommended.     

Factors involved in the determination of triglycerides in serum: An international study

Ten laboratories analysed five different specimens in duplicate on ten separate occasions by one, or several, of five common triglyceride methods. Simple statistical data are presented and, as far as possible, these are interpreted in the light of the methods used and the results of chemical analyses of the materials. Great variability was found between the results of the participating laboratories. The major factor involved seems to be the material specific nature of the methods under study. At least one method in common use is contraindicated.