Development and characterization of an adult model of obstructive hydrocephalus.

While hydrocephalus is common in adults its pathophysiology is not fully understood and its treatment remains problematic. Previous animal models have been acute, developmental, or involved non-specific blockage or inflammation and are not suitable for study of chronic adult-onset hydrocephalus. In this study, we describe the development of a canine model which allows basic physiological studies along with diagnostic and treatment procedures via surgical occlusion of the fourth ventricle with a bolus injection of cyanoacrylic gel glue. A total of 26 adult male canine mongrels were used for the induction of chronic hydrocephalus and were monitored for 1-12 weeks post-induction using magnetic resonance imaging (MRI), intracranial pressure measurements, and neurological fitness assessments. Of these, 81% (21/26) developed hydrocephalus that was mild (N = 6), moderate (N = 7), or severe (N = 8). Pressures were mild and transiently elevated, and brain compliance decreased. Clinical symptoms were also mild and transient. This model is unique in its focal obstruction without local compression or general inflammation and should facilitate the study of the pathophysiology and treatment of chronic adult-onset hydrocephalus.

Effect of cryopreservation on semen quality in patients with testicular cancer.

OBJECTIVES: Current techniques in cryopreservation of human semen substantially decrease sperm quality. In addition, the pregnancy rate using cryopreserved sperm obtained from testicular cancer patients is lower than when sperm from normal fertile men is used. However, it is still unclear whether cryopreserved sperm from these patients is inherently defective or if the sperm loses its motility after thawing. This study was undertaken to assess the effect of cryopreservation on the quality and motion characteristics of semen from patients with testicular cancer before definitive therapy compared with semen from normal volunteers. METHODS: We compared the sperm quality before and after cryopreservation in samples from 34 patients with testicular cancer and 30 normal volunteers who were referred for sperm banking over a 7-year period. The effects of cancer stage and histologic type on various semen parameters were also examined. A computer-assisted semen analysis was performed before and after cryopreservation on each specimen. The nitrogen vapor technique using Test yolk buffer with glycerol as a cryoprotective agent was used for cryopreservation. The motile sperm count and motion characteristics (motility, velocity, linearity, amplitude of the lateral head movement, motility index) were analyzed before and after cryopreservation and compared between the groups. RESULTS: Semen quality did not significantly differ among patients with Stage I, II, or III cancer. However, semen quality tended to be poorer at higher cancer stages. In general, semen quality was better among patients with pure seminomas than with pure embryonal tumors; quality was worst among patients with mixed germ cell tumors. However, 71.4% of patients with mixed tumors presented with Stage III disease, whereas all patients with seminomas presented with Stage I disease. Significant differences were also seen in prefreeze motility (median, 42% [interquartile range, 24 to 51] versus 60.5% [range, 49 to 73]; P = 0.0004) and motile sperm count (6.7 x 10(6)/mL [range, 3.4 to 14.4] versus 50.0 [range, 24.6 to 72.0]; P = 0.0001) in patients compared with controls, respectively. The motile sperm count and percent motility significantly decreased in both patients and controls after cryopreservation (P = 0.0001). However, the percentage decline in motile sperm count and motion characteristics after cryopreservation did not differ significantly between patients and controls (P > 0.01). CONCLUSIONS: We conclude that the effect of cryopreservation on sperm quality in patients with testicular cancer is identical to its effect on sperm from normal fertile men. Differences in values after preservation are explained by poor semen characteristics before freezing; semen quality declines with more extensive disease. Stage I patients also had poorer quality than control subjects. Thus, we recommend that routine sperm banking be encouraged among all patients with testicular cancer before the initiation of specific medical treatment. We also recommend that future efforts be focused on improving the technique of sperm banking.

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Differential ventricular expansion in hydrocephalus.

In the large canine model of acquired obstructive hydrocephalus that we have developed recently, computer-assisted 3-dimensional morphometry has been performed on T1-weighted Spin Echo MRI images from adult dogs before and after the induction of hydrocephalus. To date, 7 hydrocephalic animals have been analyzed that survived 7-83 days (median = 54) after receiving injections of cyanoacrylate glue into the anterior fourth ventricle. Measurements were obtained from lateral, 3rd, and 4th ventricles. The volumes of the left and right lateral ventricles were symmetrical before and after induction. Mean lateral ventricle volume increased 424% from a baseline of 0.63 cc to a post-induction value of 3.30 cc (p < 0.01 with unpaired t-test). In contrast, the 3rd ventricle expanded 187% from a mean of 0.15 cc to 0.43 cc (p < 0.05). The combined volume of the lateral and 3rd ventricles increased 369% from a mean of 0.78 cc to 3.69 cc (p < 0.01). Evans' ratios, which are used routinely in the clinical setting, were also obtained from linear measurements of the lateral ventricle width divided by brain width at the level of the foramen of Monro. These values exhibited only a 94% increase from mean baseline ratios of 0.17 to post-induction ratios of 0.33 (p < 0.05). These findings indicate that in mechanically-induced obstructive hydrocephalus the relative expansion of the lateral ventricles is greater than that of the 3rd ventricle. In addition, volumetric measurements of the lateral and 3rd ventricles suggest that the extent of ventriculomegaly is 3-4 times greater than estimated by Evans' ratios.

Cryopreservation and semen quality in patients with Hodgkin's disease.

BACKGROUND: Cryopreservation of semen from patients with Hodgkin's disease yields fewer motile sperm than from fertile men without Hodgkin's disease. However, although poor sperm quality and subfertility have been associated with Hodgkin's disease, whether the disease adversely affects sperm quality is not clear because many studies evaluated semen quality after chemotherapy or radiation therapy had begun. Furthermore, the effect of cryopreservation on semen quality in these patients is unknown. This study investigated pretreatment sperm quality and the effect of cryopreservation on semen quality in patients with Hodgkin's disease. METHODS: Specimens from 39 patients with Hodgkin's disease and 30 normal volunteers who underwent sperm banking over a 5-year period were analyzed. No patient had undergone chemotherapy or radiation therapy before sperm banking. The nitrogen vapor technique, using Test-Yolk buffer with glycerol as a cryoprotective agent, was used for cryopreservation. Prefreeze and postthaw motile sperm count (MSC) and motion characteristics, namely motility, curvilinear velocity (VCL), linearity, amplitude of lateral head movement (ALH), and motility index, were compared between the two groups. RESULTS: Prefreeze values for MSC (P = 0.0001), motility (P = 0.0001), motility index (P = 0.0001), and VCL (P = 0.0019) differed significantly between patients and donors. Except for linearity and ALH, postthaw sperm MSC, motility, VCL, and motility index decreased significantly (P = 0.0001) in both groups. However, the percentage decline in semen quality from prefreeze to postthaw values did not differ significantly between donors and patients. CONCLUSION: The pretreatment semen quality in patients with Hodgkin's disease is poor compared with that of normal fertile men. However, half the patients had a normal MSC, so a clinical diagnosis of Hodgkin's disease does not predict cryopreservation outcome adequately. Semen cryopreservation should be encouraged as a routine part of the therapeutic management of men of reproductive age who will undergo chemotherapy or radiation therapy for Hodgkin's disease.