Steady-state fluctuation and variability of betaxolol and atenolol plasma levels

Twenty-four nonsmoking male volunteers took 50 mg atenolol or 10 mg betaxolol orally once a day for 9 days in a two-period, four-sequence, randomized, crossover study. Plasma concentrations reached steady state after day 5. Percent fluctuation in plasma concentration defined as (Cmax-Cmin)/Cavg (% fluctuation 1) was 97% on day 9 for betaxolol and 343% for atenolol; thus atenolol fluctuation was more than threefold that of betaxolol. A 10-fold difference in plasma level fluctuation was observed when fluctuation was defined as (Cmax-Cmin)/Cmin (% fluctuation 2). The intersubject variances for % fluctuation 1 and % fluctuation 2 were 4.1 and 85.5 times greater for atenolol than for betaxolol; these differences were marginally statistically significant for % fluctuation 1 and significant for % fluctuation 2. The intrasubject variabilities for area under the curve and plasma level fluctuations were statistically greater for atenolol than for betaxolol. Atenolol intrasubject variances were 25 and 271 times greater than for betaxolol for % fluctuation 1 and % fluctuation 2, respectively. Thus, betaxolol exhibited less fluctuation in plasma levels with substantially less intersubject and intrasubject variability. These factors would be expected to provide a more consistent therapeutic response and more dependable dosage adjustment.     

Medroxyprogesterone acetate: variation in serum concentrations achieved with three commercially available preparations

Twenty-nine females with metastatic or locally recurrent carcinoma of the breast were treated orally with 1 g of medroxyprogesterone acetate (MPA) daily. This was used as a second- or third-line treatment. Serum concentration of MPA was measured over a 28-day period. We have demonstrated a significantly greater area-under-the-concentration-time curve, peak, and steady-state MPA concentration for Provera at 100- and 200-mg tablets (Upjohn) than for Farlutal at 500-mg tablets (Farmitalia). Relative bioavailability of preparations should be considered when prescribing or assessing treatment results when MPA is used.     

Histopathological studies on experimental marine toxin poisoning--4. Pathogenesis of experimental maitotoxin poisoning

Repeated injections of 45 ng/kg of maitotoxin into the peritoneal cavities of male ICR mice resulted in marked atrophy of lymphoid tissues, a reduction of lymphocytes in the circulating blood, reduced immunoglobulin M in serum, and an increase of calcium content in the adrenal glands. A single injection of 200 ng/kg of maitotoxin induced a marked increase in total calcium content of the adrenal glands as well as in plasma cortisol concentration (about seven times control) within 1 hr. In contrast, mice pretreated with CoCl2, a calcium channel inhibitor, and/or adrenalectomized mice, showed no discernible changes in the lymphoid tissues after repeated injections of maitotoxin. It is thus suggested that maitotoxin first stimulates calcium influx in the adrenal glands, which then causes the release of cortisol into the blood. The excess amount of cortisol in serum produces acute involution of the thymus and other lymphoid tissues.     

Predicting recurrence time of esophageal carcinoma through assessment of histologic factors and DNA ploidy

Cytophotometric analysis of nuclear DNA content was done in 128 patients with squamous cell carcinoma of the esophagus. The relationship among histopathologic features, DNA distribution pattern, and survival time was investigated from the standpoint of recurrence. Of 128 patients, 77 (60.1%) died of recurrence within 2 years after surgery: 16 (12.5%) from 2 to 5 years and two (1.6%) over 5 years. The rate of death of recurrence within 2 years was higher in patients with T4 or N1 than T1, T2, and T3 or N0 (P less than 0.01). Survivors over 5 years more frequently possessed type II DNA pattern than types III and IV (P less than 0.05). The rate of death of recurrence within 2 years was 34.4% in type II, which was lower than the 59.6% rate in type III (P less than 0.05) and the 76.6% rate in type IV (P less than 0.01). Survivors from 2 to 5 years were higher in type III than in type IV (P less than 0.05), and recurrence over 5 years was found only in type II. This inclination was more apparent in those with curative resection. In the patients with type II, careful follow-up may be needed over 5 years for late recurrence. However, in those with type IV, no recurrence over 2 years could be regarded as healed because most of their recurrences occur within 2 years. These findings suggest that the growth rate of esophageal carcinoma should reflect DNA aneuploidy, and the DNA analysis of esophageal carcinoma should be a valuable parameter for postoperative follow-up planning.     

Systemic Vasculitis with Renal Involvement — A Review

Twenty five patients with renal vasculitis presenting over an eight year period were reviewed. Ten had microscopic polyarteritis, 6 classic polyarteritis, 5 overlap syndrome, 2 Churg-Strauss syndrome and 2 Wegener’s granulomatosis. Clinical features included hypertension, pulmonary involvement, neurological involvement and arthralgia. Serum creatinine was over 500 umol/1 in 13 patients, 10 of whom required dialysis. Visceral angiography was positive in 80% of those studied, Focal and segmental necrotising glomerulonephritis was the commonest renal lesion. Treatment consisted of corticosteroids and cytotoxic agents in most cases. Plasmapheresis was used for rapidly progressive renal failure, severe pulmonary haemorrhage or cerebral vasculitis. Improvement or stabilisation of renal function was seen in 68% of patients treated. There were 4 early deaths and one late death. The diagnosis, histology, treatment and outcome of renal vasculitis is discussed. The importance of early diagnosis and treatment is emphasised in this potentially reversible cause of acute renal failure.