Risperidone and 9-hydroxyrisperidone concentrations are not dependent on age or creatinine clearance among elderly subjects

Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clearance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on concentrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 +/- 9 years (range 56-91). Mean CrCl was 55.4 +/- 32.8 mL/min/1.73 m2 (range 17-142 mL/min/1.73 m2). Mean risperidone daily dose was 1.3 +/- 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 +/- 5.3 ng/mL and 9.1 +/- 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 +/- 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperidone were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl.     

Impact of a second insemination on the results of an in vitro fertilization-embryo transfer (IVF-ET) program

In an attempt to increase the fertilization and pregnancy rates in our program, a second insemination was carried out when the first insemination yielded fewer than two fertilized oocytes. One hundred eighty consecutive patients were studied retrospectively and thirty-four required second insemination, 35% of them by donor-semen. Fifty-five and nine-tenths percent of the patients had at least one fertilized oocyte for embryo transfer, but only 21.9% of the oocytes exposed to a second insemination were fertilized. No pregnancy resulted from the transfer of oocytes fertilized by the second insemination. There were no significant correlations between the success of fertilization after a second insemination and the number of oocytes retrieved, the protocol for the induction of superovulation, or the age of the female patient. Considering that the first insemination was done at a variable time after oocyte retrieval to allow oocyte maturation, we expected all oocytes to be mature at the time of first insemination and we considered the possibility of delayed fertilization as negligible since second insemination was done at least 24–30 hr after oocyte retrieval. Even though a second insemination provides further hope for the patient, by yielding additional fertilized oocytes for embryo transfer, its main value is that it may provide additional information about male fertility.     

Serum prostacyclin binding and half-life in normal and hypertensive pregnant women

The effective half-life of prostacyclin in human serum is highly dependent on binding to serum proteins. Abnormalities in prostacyclin binding appear to be important in some patients with thrombotic thrombocytopenic purpura. We investigated prostacyclin binding and half-life in normotensive and hypertensive pregnant women and in nonpregnant controls. Pregnancy was associated with a decrease in serum prostacyclin binding and a shorter prostacyclin half-life. This decrease was even greater in women with hypertensive disorders. The decrease in prostacyclin half-life in hypertensive disorders may play an important role in the pathogenesis of these disorders. Measurement of both production and metabolism, however, will be required to adequately assess the role of prostacyclin in normal and abnormal gestation.     

The diagnostic use of the second oscillatory potential in clinical electroretinography

Of all the electroretinogram (ERG) components (a-wave, b-wave, and oscillatory potentials) only one oscillatory potential, OP₂, was found to be significantly correlated with the absolute intensity of the flash stimulus (i.e., the intensity of the stimulus irrespective of the state of retinal adaptation). Our finding was further confirmed in single cell recordings of lateral geniculate unit activity in rabbits in which peak time of OP₂ was found to correlate better with the geniculate activity. For these reasons we have identified OP₂ as the intensity coding oscillatory potential of the ERG. In order to investigate if this new feature could have some clinical significance, we examined photopic ERGs recorded from patients affected with various retinopathies. In most instances the peak time of OP₂ paralleled that of the b-wave, that is, in the ERG with delayed b-wave the peak time of OP₂ was also delayed, while in ERGs with normal b-wave peak time the peak time of OP₂ was also normal. However, in some conditions (especially in cone-rod diseases) a delayed OP₂ was found in ERGs with normal b-wave peak times.     

Urinary morbidity with a modified peripheral loading technique of transperineal (125)i prostate implantation

PURPOSE: Analysis of urinary morbidity within the first 12 months following a modified peripheral loading technique for permanent transperineal transrectal ultrasound (TRUS) guided (125)I prostate implantation and comparison of urinary morbidity with various clinical and implant parameters. MATERIALS AND METHODS: Between October 1, 1996, and March 11, 1998, 87 patients with favorable, early stage prostate cancer were treated with permanent transperineal TRUS guided (125)I prostate implantation. A peripheral loading technique was utilized for source placement with 75-80% source distribution in the periphery and 20-25% source distribution centrally. A mean total activity of 38 mCi of (125)I was implanted (range, 19-66 mCi). The mean source activity was 0.43 mCi/source (range, 0.26-0.61 mCi/source) and the mean number of sources implanted was 88 (range, 56-134). The minimum prescribed dose to the prostate was 145 Gy. The median D(90), V(100), and V(150) were 152 Gy (range, 104-211 Gy), 92% (range, 71-99%), and 61% (range, 11-89%), respectively. The median follow-up time was 19 months (range, 12-29 months). Urinary morbidity was scored at 3 weeks and then at 3-month intervals for the first 2 years using a modified Radiation Therapy Oncology Group (RTOG) grading system (scale 0-5). RESULTS: Most patients developed at least minor urinary symptoms with frequency or nocturia being the most common. Overall, 79% (69/87) of patients experienced urinary morbidity with 21% (18/87) reporting no symptoms. The incidence of overall Grade 1 urinary morbidity was 37% (32/87); Grade 2 morbidity was 37% (32/87); and Grade 3 morbidity was 6% (5/87). There was no Grade 4 or 5 morbidity. The incidence of Grade 0 frequency/nocturia was 36% (31/87); Grade 1 was 33% (29/87); Grade 2 was 30% (26/87); and Grade 3 was 1% (1/87). Grade 0 dysuria was seen in 56% (49/87) of patients; 32% (28/87) had Grade 1; 10% (9/87) Grade 2; and 1% (1/87) Grade 3 dysuria. Most urinary symptoms started a few weeks after implantation and began to subside by 6 months. At 12 months, 22% (19/87) of patients had persistent urinary symptoms (78% Grade 0, 15% Grade 1, 3% Grade 2, and 3% Grade 3). The mean urethral point dose was 174 Gy (range, 99-315 Gy). The mean number of sources implanted correlated significantly with the likelihood of developing acute urinary morbidity (p = 0.03). The total activity implanted also correlated with the morbidity outcome dysuria (p = 0.01) with a threshold seen at 37 mCi. Urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage did not correlate with morbidity. CONCLUSIONS: Permanent transperineal TRUS guided (125)I prostate implantation using a modified peripheral loading technique is associated with mild urinary morbidity that resolves in 78% of patients by 12 months. Grade 3 urinary morbidity was encountered in only 6% (5/87) of patients. Urinary morbidity may be related to the total number of sources implanted and/or the total activity implanted. Overall urinary morbidity was not correlated with urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage. The low incidence of urinary morbidity may be a consequence of our modified peripheral loading technique and/or the selection of patients with good-to-excellent preimplant urological parameters. Longer follow-up is necessary to assess biochemical control rates and long-term morbidity.     

Cellular blue nevus ("melanocytoma") of the spinal meninges: electron microscopic and immunohistochemical features

A primary cellular blue nevus (melanocytoma) of the spinal canal in a 21-year-old woman is reported. Light microscopic examination revealed a melanotic neoplasm with histological patterns resembling schwannoma, dermal nevi, and neuroblastic-like tumor. The ultrastructural features of the neoplastic cells were similar to those in dermal blue nevi and melanomas. There was no evidence of arachnoidal cell differentiation. Immunohistochemistry revealed positive reactions for S-100 protein and neuron-specific enolase in many cells and no reactions for glial fibrillary acidic protein, cytokeratins, epithelial membrane antigen, 70-kD neurofilament protein, or Leu-7. Vimentin was strongly positive in the melanocytic cells as well as in the arachnoidal cells of involved meninges. The ultrastructural and immunohistochemical features support the nevoid nature of this tumor, which is frequently mislabeled as "melanotic meningioma."