Lack of anticonvulsant tolerance with RU 32698 and Ro 17-1812

Possible development of anticonvulsant tolerance to three benzodiazepine receptor ligands was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. Extensive tolerance developed rapidly in the case of diazepam (0.35 mg/kg b.d. or 1.5 mg/kg b.d.). No significant tolerance was seen with the imidazopyrimidine derivative RU 32698 (9 mg/kg b.d.) or the partial agonist benzodiazepine Ro 17-1812 (1 mg/kg b.d.) These results provide further support for the hypothesis that partial agonists at the benzodiazepine receptor induce less tolerance than full agonists.     

Expert system-controlled image display

Conventional computer-based medical expert systems deliver advice to physicians as written text. While such advice is useful, it has distinct limitations in a visually oriented discipline such as diagnostic radiology, in which decisions often depend on pattern recognition and appreciation of subtle morphologic features. The authors developed a prototype expert computer system, IMAGE/ICON, which displays groups of images sorted into a series of axes based on different ways in which they may be similar. They may share a common feature, group of features, causes, or clinical setting. IMAGE/ICON may display examples of morphologic variations of a dominant finding or a spectrum of abnormalities seen in an specific disease or group of diseases. The system also assembles a written analysis of key features of a case. Such a tool may be useful as a diagnostic aid or for continuing medical education. It is likely to have particular impact in the form of an intelligent radiologic workstation, as picture archiving and communication systems become available.     

Clinical use of rapid T2 weighted partial saturation sequences in MR imaging

Rapid T2 dependent field echo [partial saturation (PS)] sequences were used in 38 patients with brain tumors, intracerebral hematomas, and cerebral infarction as well as other neurological and abdominal disease. Reduction in the radiofrequency excitation angle (alpha) from 90 to 30 degrees produced an increase in lesion contrast as did change of echo time (TE) from 33 to 59 or 120 ms using repetition time (TR) values in the range of 120-500 ms. The PS sequence showing most lesion contrast was compared with conventional spin echo (SE 1,500/80 and SE 1,500/120) and inversion recovery (IR 1,500/500/44 and IR 1,500/100/44) sequences. Although PS sequences with TE = 39 ms were usually inferior to conventional SE sequences, those with TE = 59 or 120 ms were comparable and in some cases (particularly hematomas) superior. The PS sequences with alpha of approximately 30 degrees, TR of 80-250 ms, and TE of 60-120 ms offer considerable savings in time compared with conventional sequences although more work will be required to explore the limits of this approach and to optimize sequences at different field strengths.     

Two or six hyperthermia treatments as an adjunct to radiation therapy yield similar tumor responses: results of a randomized trial

From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia-radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.     

Calcium carbonate is an effective phosphate binder when dialysate calcium concentration is adjusted to control hypercalcemia

The efficacy of calcium carbonate (CaCO3) as a phosphate binder has been limited by its tendency to cause hypercalcemia. Since standard dialysate calcium concentrations (3.0-3.5 mEq/l) increase the risk of developing hypercalcemia with large doses of CaCO3 by inducing positive calcium balance during hemodialysis (HD), we compared control of hyperphosphatemia in 41 HD patients during 4 months each of aluminum hydroxide (Al(OH)3) and CaCO3 when the dialysate calcium concentration was lowered, as required, to maintain the predialysis serum calcium concentration within the normal range. Mean predialysis serum phosphorus and calcium concentrations were 5.0 +/- 0.2 mg/dl and 9.3 +/- 0.1 mg/dl, respectively, during 4 months CaCO3 (9.2 +/- 0.3 g/day) and 4.9 +/- 0.2 g/dl and 9.1 +/- 0.1 mg/dl during the previous 4 months Al(OH)3 therapy (2.9 +/- 0.2 g/day). Reducing the dialysate calcium concentration to below 3.0 mEq/l (mean 2.1 +/- 0.04) in the 11 patients who developed hypercalcemia on CaCO3 decreased serum calcium (-1.1 +/- 0.15 mg/dl) and ionized calcium (-0.3 +/- 0.04 mEq/l) during HD, enabled CaCO3 (8.8 +/- 0.4 g/day) to be continued, and maintained predialysis serum calcium and phosphorus at 10.4 +/- 0.1 mg/dl and 5.2 +/- 0.3 mg/dl, respectively. No improvement in acidosis or biochemical hyperparathyroidism was observed during CaCO3 therapy but serum aluminum was significantly decreased after CaCO3 (p less than 0.005). We conclude that CaCO3 prevents interdialytic hyperphosphatemia as effectively as Al(OH)3 without increasing the predialysis serum calcium x phosphorus product, provided serum calcium is maintained within the normal range by adjusting the dialysate calcium concentration.     

Multiple pterygium syndrome: a case complicated by malignant hyperthermia

The autosomal recessive multiple pterygium syndromes are a heterogeneous group of disorders in which multiple joint contractures are associated with cutaneous webbing. Recently, we evaluated a 33 week gestation male in whom multiple pterygia were one feature of a broader pattern of malformation. Clinical management was adversely affected by malignant hyperthermia. In this report we present the clinical, radiographic and pathologic data of this patient and those of an affected stillborn female sibling. We believe that these represent the features of a newly recognized disorder.     

A case of quadrantic capillaropathy

A case of transient pigmented purpuric dermatosis in an unusual segmental distribution is presented, and possible aetiological factors discussed.