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Biomedical subjects

C J Kane

Publications and source records attributed to C J Kane.

At least 37 records · Page 2Linked to original sources
PubMed1998

Microglia, but not astrocytes, react to sciatic nerve injury in aging rats.

Peripheral nerve axotomy activates microglia and astrocytes within regions of brainstem or spinal cord from which the nerve arises. The present study demonstrates that unilateral sciatic axotomy in rats 2 to 18 months of age results in differing responses with age between these two glial populations. By 4 days postaxotomy, both astrocytes and microglia become activated in 2-month-old rats, whereas only the microglial population shows evidence of activation in rats 8 to 18 months of age.

Aging↗
PubMed1998

The fate of 10-year clinically recurrence-free survivors after definitive radiotherapy for T1-3N0M0 prostate cancer.

We recently reported the outcome of 168 patients treated with pelvic lymphadenectomy and definitive radiation therapy. This report is a subanalysis of those patients (pts) who were clinically without evidence of disease (NED) 10 years after a negative staging pelvic lymphadenectomy and definitive radiation therapy for prostate cancer. One hundred of our original cohort of 168 patients had at least ten year follow-up. 76 patients had pathologically negative lymph nodes and had not received hormonal therapy. Forty-two N0 patients with sufficient follow-up were alive and clinically NED 10 years post-operatively. Distribution by disease stage at diagnosis was: Stage A2: 12 pts; Stage B: 19 pts; Stage B2/C: 6 pts; Stage C: 5 pts. Median follow-up was 13.3 years, with a minimum follow-up of 10 years. Of the 42 patients clinically NED at 10 years, 5 pts died subsequently without PSA data, remaining clinically NED a median of 13 y 3 m postoperatively; 37 patients were alive and without evidence of disease off all therapy at 10 years post-operatively. Bone scans were performed on 8 of the 9 patients with PSA over 4.0 ng/ml or on hormonal therapy. These revealed a single patient with diffuse but asymptomatic bone metastases. Ultrasound-guided sextant biopsies were performed on one 78-year-old patient with elevated PSA 19 years post-operatively, revealing an asymptomatic local recurrence. Patients who survive clinically NED for 10 years have a low likelihood of clinical failure, even in the presence of PSA values between 4.0 and 10 ng/ml. In these patients, PSA trends are of greater utility than absolute values.

Disease-Free Survival↗
PubMed1998

Prospective comparison of unenhanced spiral computed tomography and intravenous urogram in the evaluation of acute flank pain.

OBJECTIVES: To prospectively compare the diagnostic ability of unenhanced spiral computed tomography (NCCT) and intravenous urogram (IVU) in the evaluation of adults with acute flank pain. METHODS: After giving informed consent, 106 adult patients with acute flank pain suspected of having urolithiasis underwent NCCT followed by IVU. Subsequent follow-up was scheduled within 72 hours in the Urology Clinic. Each NCCT was read by a single radiologist who was unaware of clinical history and IVU results. Each IVU was read by a different radiologist who was unaware of clinical history and NCCT results. Sensitivity, specificity, and positive and negative predictive values were determined for NCCT and IVU. RESULTS: The diagnosis of ureterolithiasis was defined as unequivocal evidence of urolithiasis on either NCCT or IVP. Seventy-five of 106 patients evaluated were diagnosed with ureterolithiasis. Clinical follow-up was available in 74 (98%) stone patients and in 31 (100%) of 31 non-stone patients. In 72 of the 75 patients diagnosed with ureteral calculi, the NCCT made the diagnosis. IVU made the diagnosis in 65 of the 75 patients. Of the 31 patients without ureterolithiasis, the NCCT was negative in all cases. IVU was negative in 29 of the 31 cases. Unenhanced spiral CT was 96% sensitive and 100% specific (P <0.001). IVU was 87% sensitive and 94% specific (P <0.001). Compared with IVU, using the log odds ratio and Fisher's exact test, NCCT was significantly better able to predict the presence of urolithiasis (P=0.015). CONCLUSIONS: NCCT accurately diagnoses ureterolithiasis in patients presenting with acute flank pain. NCCT is significantly better than IVU in determining the presence of urolithiasis.

Acute Disease↗
PubMed1998

Intragastric intubation: important aspects of the model for administration of ethanol to rat pups during the postnatal period.

One technique for the controlled delivery of ethanol to neonatal rat pups is intragastric intubation. Often, the vehicle used for delivery of ethanol is composed of a nutrient mixture to compensate for decreased suckling or other possible nutritional compromise. This study analyzed the selection of nutrient vehicle, the combination of experimental treatment groups within a litter, and the overall litter size on the growth rate of ethanol-intubated and intubated-control pups, compared with mother-raised control pups. Sprague-Dawley rat pups were raised in litters of 8 or 10, and administered ethanol by intragastric intubation with 20% (v/v) Sustacal or 80% (v/v) Intralipid-II nutrient vehicle. Pups were treated between postnatal days 2 and 10, and body weight was analyzed on day 10. Pups were assigned to a treatment group as either intubated ethanol, intubated control, or nonintubated mother-raised controls. Experimental comparison by statistical analyses was performed to identify the optimal treatment design (mixed treatment groups in a single litter or a single treatment group per litter), the optimal vehicle (Sustacal or Intralipid-II), and the optimal number of pups per litter (8 vs. 10). The analyses demonstrate that the mixing of intubated control, intubated ethanol, and nonintubated mother-raised control treatment groups within a single litter introduced an uncontrolled variable that confounded measurement of ethanol-specific alterations. The sensitivity of treatment groups to inclusion in mixed litters was dependent on the nutrient vehicle and thus nutritional adequacy. Our results suggest that an optimal design was achieved with eight pups per litter. Furthermore, ethanol intubated and intubated control pups grow at a rate identical to parallel litters of eight mother-raised control pups when Intralipid-II is used as nutrient vehicle, and a single treatment group is present in a litter. Optimization of these experimental parameters has provided an excellent neonatal rat model for analysis of specific ethanol effects on brain development during the third trimester.

Animals↗
PubMed1998

Second primary malignancies in T1-3N0 prostate cancer patients treated with radiation therapy with 10-year followup.

PURPOSE: The risk of patients with prostate cancer to have second primary malignancies is unclear. Population and autopsy based studies have shown no increased risk, which is at variance with several institutional analyses. A retrospective review was performed with comparison to expected cancer data from the Connecticut Tumor Registry. MATERIALS AND METHODS: Records of a cohort of prostate cancer patients treated with staging pelvic lymphadenectomy and definitive radiotherapy between November 1, 1974 and July 7, 1987 were reviewed. Median potential followup from date of diagnosis was 10.9 years. RESULTS: Of the 164 patients 150 (91.5%) had followup to death or to August 1995, with data available in part on 4 of the remaining patients. In 43 patients 51 second primary malignancies developed. Increased frequency of lymphomas, and kidney, bladder and rectal lesions (all p < 0.001) was observed concurrently with diagnosis of prostate cancer, although this may be due to bias since full staging for the prostate cancer may have led to their diagnosis. An increased frequency of renal lesions in the 1 to 4-year followup period (p = 0.032) also was observed. Two sarcomas and a leukemia were putatively radiation induced but their frequency was not significantly different from the comparison baseline. CONCLUSIONS: Much of the apparent increase in second primary malignancies associated with prostate cancer noted by some authors may be attributed to bias in the staging process. Renal cancers may occur more frequently in patients with prostate cancer but the distribution of these lesions is inconsistent with a field defect mechanism of cancer induction.

Aged↗
PubMed1997

Transforming growth factor-beta2 selectively alters the developmental expression of the fast transient A-current in cultured rat superior cervical ganglion neurons.

Cultures of neonatal rat superior cervical ganglion (SCG) were utilized to examine the ability of transforming growth factor-beta2 (TGFbeta2) to alter voltage-gated K+ channel development. Whole-cell patch clamp recordings were used to monitor changes in three separate K+ currents: A rapidly inactivating A-current (I(Af)), a slowly inactivating A-current (I(As)), and a non-inactivating current (I(K)). Continuous TGFbeta2 (10 ng/ml) treatment selectively altered the normal developmental decrease in I(Af) expression in SCG neurons, but did not significantly change I(As) or I(K) expression. After 2 weeks of treatment, the mean I(Af) current density in control cultures had decreased 67%, while the I(Af) current density in TGFbeta2 treated cultures remained near initial values (approximately 2.7-fold higher than control). This difference remained even after 4 weeks of exposure. TGFbeta2 did not appear to change the activation kinetics or voltage-dependence of I(Af). These findings indicate that TGFbeta2 may play an important role in modulating the development of neuronal excitability by regulating the expression of voltage-gated K+ channels.

Animals↗
PubMed1997

Astrocytes in the aged rat spinal cord fail to increase GFAP mRNA following sciatic nerve axotomy.

Aging in the brain is associated with specific changes in the astrocyte population. The present study establishes that similar changes occur in the aging spinal cord. The levels of glial fibrillary acidic protein (GFAP) mRNA were significantly increased 0.4-fold in aged 8- to 17-month-old rats compared to young 2-month-old rats. The ability of astrocytes in the aging spinal cord to respond to a non-invasive CNS injury was compared to young rats 4 days following sciatic nerve axotomy. The level of GFAP mRNA was significantly increased 0.5-fold in the young rats in response to axotomy. In contrast, the level of GFAP mRNA in aged rats did not increase following injury above that present in non-axotomized rats of the same age.

Aging↗
PubMed1997

Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord.

A prominent role for phagocytic cells in the regenerative response to CNS or PNS injury has been suggested by numerous studies. In the present work we tested whether increasing the presence of phagocytic cells at a spinal cord injury site could enhance the regeneration of sensory axons from cut dorsal roots. Nitrocellulose membranes treated with TGF-beta or coated with microglial cells were cotransplanted with fetal spinal cord tissue into an injured adult rat spinal cord. Cut dorsal roots were apposed to both sides of the nitrocellulose. Four weeks later, animals were sacrificed and spinal cord tissue sections were processed for immunocytochemical detection of calcitonin gene-related peptide (CGRP-ir) to identify regenerated sensory axons. Adjacent sections were processed with the antibody ED-1 or the lectin GSA-B4 for detection of macrophage/microglial cells in association with the regrowing axons. Qualitative and quantitative data indicate a correlation between the pattern and extent of axonal regeneration and the presence of phagocytic cells along the nitrocellulose implant. Axonal regeneration could be experimentally limited by implanting a nitrocellulose strip treated with macrophage inhibitory factor. These results indicate that increasing the presence of activated macrophage/microglial cells at a spinal cord injury site can provide an environment beneficial to the promotion of regeneration of sensory axons, possibly by the release of cytokines and interaction with other nonneuronal cells in the immediate vicinity.

Animals↗
PubMed1997

Microencephaly and selective decreases in cerebellar Purkinje cell numbers following combined exposure to ethanol and methadone during rat brain development.

This study evaluated the neuroanatomical effects of combined ethanol and methadone exposure on cerebellar development. Ethanol, methadone or a combination of both drugs was delivered twice daily to rat pups using intra-gastric intubation from postnatal day 6 (PN6) to PN10 inclusive. The intubated control group (IK) received equal volumes of isocaloric vehicle. Purkinje cell numbers in cerebellar lobules I-X were quantified from midsagittal sections of the cerebellar vermis at PN11. Deficits of 15-23% in body, total brain, cerebrum, cerebellum and brainstem weights were exhibited for the ethanol/methadone-treated (IEM) group compared to IK. Purkinje cell deficits resulting from IEM treatment were found in lobules VI through X compared to IK with significant decreases of 31 and 23%, respectively, for lobules VIII and X. In contrast, neither ethanol nor methadone exposures under these treatment conditions caused cerebellar deficits.

Animals↗
PubMed1997

Renal imaging with spiral CT scan: clinical applications.

Spiral computed tomography (CT) is an imaging modality that utilizes the rapid acquisition of cross-sectional data that can be reconstructed in a number of useful ways. We briefly describe the technology of spiral CT and recent advancements that have made spiral CT feasible. The advantages over conventional CT and angiography are reviewed. Urologic clinical applications are discussed including: detection of a crossing vessel prior to endopyelotomy for ureteropelvic junction (UPJ) obstruction, evaluating renal vascular anomalies preoperatively, and assistance in preoperative planning prior to partial nephrectomy in benign and malignant disease. Spiral CT has numerous advantages over conventional CT and angiography, and will likely have a notable role in future renal imaging.

Adult↗
PubMed1996

Transforming growth factor-beta 2 both stimulates and inhibits neurogenesis of rat cerebellar granule cells in culture.

Transforming growth factor-beta 2 (TGF beta 2) is expressed in the developing cerebellar cortex during the period of granule cell proliferation and maturation. However, the role of TGF beta 2 in granule cell development is confused by conflicting observations regarding TGF beta 2 control of neurogenesis. To resolve these conflicts and determine the effect of TGF beta 2 on neurogenesis, rat cerebellar granule cell cultures were treated with TGF beta 2 (0.1-100 ng/ml, 24 h) in the presence or absence of exogenous serum. Neuroblast proliferation was quantified by bromodeoxyuridine and [3H]thymidine incorporation. TGF beta 2 stimulated proliferation to 220% of controls in the presence of serum (ED50 = 0.4 ng/ml) based on bromodeoxyuridine labeled granule cell counts. In contrast, in serum free medium, TGF beta 2 inhibited proliferation 75% (ED50 = 0.7 ng/ml). DNA synthesis measured by [3H]thymidine incorporation was increased to 122% in the presence of serum factors, but inhibited 70% in serum free medium, as a result of TGF beta 2 activity. Thus, TGF beta 2 differentially regulates neurogenesis of cerebellar granule cells depending on the presence of exogenous, undefined regulatory factors derived from serum. This suggests that TGF beta 2 activity in cerebellar neurogenesis is complex as it may be modulated by the repertoire of other endogenous regulatory factors in the developing cerebellar cortex.

Animals↗
PubMed1996

Proliferation of astroglia from the adult human cerebrum is inhibited by ethanol in vitro.

Chronic alcoholism is associated with atrophy of the adult brain, while fetal exposure to ethanol can cause microencephaly. Since astroglial pathology is a common feature of ethanol exposure in both humans and animal models, the direct influence of ethanol on proliferation of human astroglia from the gray and white matter of adult temporal lobe was determined and compared. Astroglial cultures were exposed to constant concentrations of ethanol at realistic social and clinical levels (0.1, 0.2 or 0.5%; w/v) for 1 to 5 days. Proliferation was quantified by bromodeoxyuridine labeling and enumeration of replicating cells. Ethanol exposure significantly inhibited proliferation of both gray and white matter astroglia in a dose and duration dependent manner. Gray matter was slightly more sensitive than white matter to inhibition by low to moderate concentrations of ethanol; in contrast, white matter was more sensitive to high ethanol concentrations. Maximum inhibition was 20% in gray matter and 25% in white matter. Human astroglial proliferation was directly inhibited in the absence of neurons, microglia, neuronal degeneration or systemic factors that have confounded in vivo studies. Restricted astroglial proliferation may underlie aspects of the astroglial pathology associated with ethanol exposure.

Adult↗
PubMed1996

Transforming growth factor-beta2 increases NMDA receptor-mediated excitotoxicity in rat cerebral cortical neurons independently of glia.

The ability of transforming growth factor-beta2 (TGFbeta2) to directly regulate neuronal sensitivity to glutamate and N-methyl-D-aspartate (NMDA) excitotoxicity in rat cerebral cortical neurons was investigated. Mixed neuronal-glial cultures treated with TGFbeta2 (1-10 ng/ml) exhibited a significant 25-50% increase in neuronal death compared to control cultures. TGFbeta2 potentiation of this endogenous glutamate excitotoxicity was blocked by the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate. In addition, neuronal death induced by brief NMDA exposure in both mixed neuronal-glial and pure neuronal cultures was increased by TGFbeta2 (1-30 ng/ml) with a similar dose-response curve. These findings indicate that TGFbeta2, at physiologically relevant concentrations, potentiates NMDA receptor-mediated excitotoxicity and that this occurs independently of TGFbeta2 effects on glia.

2-Amino-5-phosphonovalerate↗
PubMed1996

Ultrasonographic appearance of necrotizing gangrene: aid in early diagnosis.

In 2 seriously ill patients with scrotal swelling of uncertain origin, scrotal and perineal ultrasonography demonstrated gas in the soft tissue before crepitus was detected on physical examination. Necrotizing infections of the scrotum and perineum have characteristic ultrasonographic features that can facilitate earlier diagnosis and treatment.

Aged↗
PubMed1996

Voiding dysfunction in human immunodeficiency virus infections.

PURPOSE: We prospectively evaluated the current spectrum of urodynamic pathology in patients infected with human immunodeficiency virus (HIV) who presented with voiding dysfunction. MATERIALS AND METHODS: We obtained a directed genitourinary and neurological history, and performed a physical examination and urodynamic testing in 18 patients. A 4-channel membrane urethral catheter was used to record intravesical and intraurethral pressures simultaneously. RESULTS: Detrusor hyperreflexia was present in 28% of our patients and detrusor-sphincter dyssynergia in 28%. Detrusor areflexia, previously described as the most frequent abnormality, was uncommon in our series (6% of patients). CONCLUSIONS: This changing proportion of urodynamic diagnoses may reflect a changing pattern of neurological manifestations of HIV infection due to more aggressive management. Urodynamic evaluation remains critical for precise diagnosis and treatment in patients with HIV who present with urinary symptoms.

Adult↗