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Biomedical subjects

J W Brock

Publications and source records attributed to J W Brock.

At least 19 recordsLinked to original sources

Evaluation of renal resistive index, maximum velocity, and mean arterial flow velocity in a hydronephrotic partially obstructed pig model.

RATIONALE AND OBJECTIVES: The authors investigate, in a controlled pig model, the usefulness of Doppler sonographic measurements of resistive index (RI), maximum velocity (Vmax), and mean velocity (Vmean) in diagnostic evaluation of the partially obstructed kidney. METHODS: Seven female pigs underwent surgical partial unilateral renal obstruction at the ureteropelvic junction. Doppler parameters of RI, Vmax, and Vmean were measured preoperatively and postoperatively in obstructed and contralateral nonobstructed kidneys. The General Linear Model multivariate analysis of variance was used for statistical analysis of data. RESULTS: There was no significant difference in the preoperative control values of RI (P = 0.71), Vmax (P = 0.27), and Vmean (P = 0.12). There was a statistically significant decrease in the Vmax and Vmean after postoperative day 5 in the obstructed kidney compared with the contralateral nonobstructed kidney (P = 0.01 and 0.03, respectively). There was no statistically significant difference in RI during the study. CONCLUSIONS: In this study, RI was not a reliable indicator of partial renal obstruction. Measurements of maximal and mean blood flow velocities reached discriminatory significance only after the fifth postobstructive day, proving insensitive in the immediate postobstructive period. Vmax and Vmean demonstrated a decrease in the partially obstructed renal collecting system after 5 days of obstruction and may serve as useful parameters in the evaluation of obstruction after the immediate acute period, when compared with a nonobstructed contralateral system.

Animals

Preclinical experiences with magnetic drug targeting: tolerance and efficacy.

Although site-specific direction of drugs within an organism would benefit patients with many diseases, active drug targeting is clinically not yet possible. To overcome some of the problems associated with active drug targeting, we have developed a magnetic fluid to which drugs, cytokines, and other molecules can be chemically bound to enable those agents to be directed within an organism by high-energy magnetic fields. In the first part of this study, various concentrations of the magnetic fluid were tested in rats and immunosuppressed nude mice with regard to subjective and objective tolerance. In the second part, the same parameters were evaluated after administration of the ferrofluid to which epirubicin (4'-epidoxorubicin) was chemically bound. Finally, two forms of therapy with the magnetic fluid were tested: tumor treatment by mechanical occlusion with the ferrofluid in high concentrations; and magnetic drug targeting, using small amounts of the ferrofluid as a vehicle to concentrate epirubicin locally in tumors. As a result, the ferrofluid did not cause major laboratory abnormalities; there was no LD50. With very high concentrations of the ferrofluid, animals showed lethargy for 1-2 days. There were no intolerances with the epirubicin-bound ferrofluid as well. Both forms of treatment led to complete tumor responses in an experimental human kidney as well as in a xenotransplanted colon carcinoma model. Thus, the magnetic fluid is a safe agent, which can be used in different ways for local forms of cancer treatment in conjunction with high-energy magnetic fields.

Animals

Evidence for genetically mediated dysfunction of the central dopaminergic system in the stargazer rat.

The stargazer rat is an autosomal recessive mutant (homozygous stg/stg) that displays abnormal behavior, characterized by stereotypic head-movement, circling, and a high level of ambulatory activity. Heterozygous (stg/+) littermates display normal spontaneous behaviors. In this study, stargazers and their unaffected littermates were compared in their behavioral responses to both stimulation and inhibition of dopamine D2/D3 receptors, using quinpirole and haloperidol. Stargazers were observed to yawn a significantly fewer number of times than littermates in response to (--)-quinpirole (50 mu g/kg, IP). Haloperidol (HAL 0.1 mg/kg and 0.3 mg/kg, SC) caused a decrease in stereotypic head-movement in the mutants that was both time- and dose-dependent. In normal littermates, HAL inhibited locomotor activity and produced catalepsy in a time- and dose-dependent manner. In stargazers, both doses of HAL inhibited locomotor activity to a similar degree as in the littermates. However, no catalepsy was detectable in the mutants using 0.1 mg/kg of HAL. A dose of 0.3 mg/kg HAL was only weakly cataleptogenic. Overall, the spectrum of abnormal behaviors expressed by the stargazers and the present evidence of D2/D3 receptor subsensitivity suggest that stargazers possess a genetically mediated dysfunction of the central dopaminergic system.

Animals

Continuous caudal anaesthesia with chloroprocaine as an adjunct to general anaesthesia in neonates.

PURPOSE: The authors prospectively evaluated the use of a continuous caudal epidural infusion of chloroprocaine as an adjunct to general anaesthesia during intra-abdominal surgery in neonates. CLINICAL FEATURES: The technique was used in 25 neonates ranging in age from 1 to 28 days and in weight from 2.2 to 4.9 kg. Following anaesthetic induction and tracheal intubation, an initial bolus dose of chloroprocaine 3% (1 or 1.5 ml.kg-1) was followed by a continuous infusion of 1 or 1.5 ml.kg-1.hr-1 administered through a caudal epidural catheter. No parenteral opioids were administered. The duration of the surgical procedures varied from one hour five minutes to three hours 15 min. The first three neonates received a bolus dose of 1.0 ml.kg-1 followed by an infusion of 1.0 ml.kg-1.hr-1 chloroprocaine 3%. These three neonates required an additional bolus dose followed by an increase in the infusion to 1.5 ml.kg-1.hr-1 to provide surgical anaesthesia. Adequate intraoperative anaesthesia was achieved in all 25 neonates with an infusion of 1.5 ml.kg-1.hr-1 of chloroprocaine 3%. This was evidenced by a lack of haemodynamic response to surgical manipulation. No neonate required more than 0.2% isoflurane or 70% nitrous oxide in oxygen. No episodes of haemodynamic instability (decreased blood pressure/bradycardia) related to the caudal epidural anaesthesia were noted. Twenty-three of 25 of the neonates' tracheas were extubated immediately (within 10 minutes) following the surgical procedure. CONCLUSIONS: Caudal anaesthesia with a continuous infusion of chloroprocaine can be used as an adjunct to general anaesthesia during abdominal surgery in neonates. Our initial experience suggests that the combined technique may eliminate the need for parenteral opioids and limit the intraoperative requirements for inhalational anaesthetic agents.

Anesthesia, Caudal

A rat homolog of the mouse deafness mutant jerker (je).

An autosomal recessive deafness mutant was discovered in our colony of Zucker (ZUC) rats. These mutants behave like shaker-waltzer deafness mutants, and their inner ear pathology classifies them among neuroepithelial degeneration type of deafness mutants. To determine whether this rat deafness mutation (-) defines a unique locus or one that has been previously described, we mapped its chromosomal location. F2 progeny of (Pbrc:ZUC x BN/Crl) A/a B/b H/h +/- F1 rats were scored for coat color and behavioral phenotypes. Segregation analysis indicated that the deafness locus might be loosely linked with B on rat Chromosome (Chr) 5 (RNO5). Therefore, 40 -/- rats were scored for BN and ZUC alleles at four additional loci, D5Mit11, D5Mit13, Oprd1, and Gnb1, known to map to RNO5 or its homolog, mouse Chr 4 (MMU4). Linkage analysis established the gene order (cM distance) as D5Mit11-(19.3)-B-(17.9)-D5Mit13-(19. 2)-Oprd1-(21.5) - (1.2) Gnb1, placing the deafness locus on distal RNO5. The position of the deafness locus on RNO5 is similar to that ofjerker (je) on MMU4; the phenotypes and patterns of inheritance of the deafness mutation and je are also similar. It seems likely that the mutation affects the rat homolog of je. The rat deafness locus should, therefore, be named jerker and assigned the gene symbol Je.

Animals

Changes in monoamines and their metabolite concentrations in REM sleep-deprived rat forebrain nuclei.

Rapid eye movement sleep deprivation (REMSD) is a potent stressor in rats. Behavioral abnormalities such as passive and active avoidance, locomotor activity, problem solving, sensory information processing, and the development of adaptive copping strategy in response to repeated stress are among the earliest obvious symptoms of REMSD, the mechanism for which remain largely unknown. The aim of this study was to determine whether 96 h of REMSD causes changes in monoamine neurotransmitters concentrations in rat forebrain regions (frontal cortex, FC; parietal cortex, PC, and striatum) that are involved in mediating higher brain functions such as attentional mechanisms, sensory information processing, and locomotor activity, which are severely affected in REMSD conditions. Rats were subjected to 96 h of REMSD using inverted flower pot water tank technique. To account for the stress associated with water tanks, a tank control group (TC) was included where the animals could reside comfortably on a large pedestal in the water tank. Regional brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenyacetic acid (DOPAC), L-3,4-dihydroxyphenylalanine (L-DOPA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (HIAA) were determined by electrochemical detection using high-performance liquid chromatography. The concentrations of serotonin and its metabolite, HIAA, was reduced in the frontal and parietal cortexes of REMSD rats compared with TC or cage control (CC) group. NE, DA, DOPAC, and HVA concentrations in FC and PC of REMSD animals were remained unchanged compared with TC or CC rats. A significant increase in the concentrations of DA metabolites was observed in the striatum of REMSD rats when compared with CC and TC rats. There was a 29 and 31% increase in the concentration of striatal DA in REMSD group compared to the TC and CC groups, respectively; however, these percentages were not statistically different. Striatal NE, 5-HT, and HIAA concentrations were not significantly different among the three groups. These results suggest that 96 h of REMSD alters dopaminergic and serotonergic systems in different locations in rat brain. The effect of REMSD on the serotonergic systems are localized in the cerebral cortex, whereas dopaminergic metabolism is increased in the striatum.

Animals

Laparoscopic evaluation for contralateral patent processus vaginalis: Part II.

Between May 1,1992 and August 1, 1995, 599 consecutively treated children under 10 years of age evaluated by the authors for a known inguinal hernia were involved in a prospective protocol to determine whether diagnostic laparoscopy has a place for evaluation of the contralateral inguinal region. The experience with the first 221 patients was reported at the 1993 AAP meeting. In this total experience, 81 patients had known bilateral inguinal hernias and did not require diagnostic laparoscopy. Five hundred eighteen patients had a unilateral inguinal hernia with the status of the contralateral region being unknown. Between May 1, 1992 and May 1, 1994, 368 children underwent evaluation using an umbilical approach. However, for the past 14 months, 150 patients have undergone the diagnostic laparoscopy through the ipsilateral hernia sac. Among the children under 1 year of age, 98 were found to have a unilateral hernia and also a contralateral patent processus vaginalis (CPPV) and 110 had a unilateral hernia. Of the children older than age 1,116 had a unilateral hernia and CPPV and 194 had only a single hernia. After induction of anesthesia, it was suspected on clinical examination that 195 of the 518 patients had a CPPV. However, laparoscopy showed that only 94 (48%) had a CPPV. In the remaining 323 patients, the surgeon believed that a CPPV was not present based on the examination. This negative finding was verified in only 198 patients (81%), but a surprising 125 (39%) did have CPPV documented at the time of endoscopy. Insufflation alone was very unrellable for documenting the presence of CPPV. Of the 214 patients for whom CPPV on the contralateral side was documented during laparoscopy, only 41 (19%) had a positive finding on insufflation. This experience has convinced the authors that diagnostic laparoscopy is the most accurate means to ascertain whether a patient should undergo contralateral inguinal exploration. In addition, laparoscopy through the ipsilateral inguinal sac is now the preferred approach.

Female

Unilateral hydronephrosis in infants: are measurements of contralateral renal length useful?

PURPOSE: We investigated whether measurement of contralateral renal length in newborns with unilateral hydronephrosis may help to assess clinically significant hydronephrosis in the affected kidney. MATERIALS AND METHODS: We reviewed our experience with 53 newborns who had unilateral hydronephrosis presumed secondary to ureteropelvic junction obstruction. We divided the patients according to the presence of mild hydronephrosis and no obstruction on a furosemide renogram, severe hydronephrosis and obstruction on a furosemide renogram or a unilateral multicystic kidney. RESULTS: We found no significant correlation between findings on the affected and opposite normal sides. Contralateral hypertrophy, hypotrophy and normal sized kidneys were frequent findings. CONCLUSIONS: We conclude that measurement of contralateral renal length is not helpful in the evaluation of newborns with unilateral hydronephrosis.

Humans

Penile orthoplasty using dermal grafts in the outpatient setting.

OBJECTIVES: To review and evaluate our extensive outpatient experience in the use of dermal grafts for the correction of significant residual chordee in patients requiring penile orthoplasty. METHODS: The medical records of all patients requiring surgical correction for severe penile curvature over the past 5 years were reviewed. Among these, 51 patients were identified in whom dermal grafts were used to correct severe residual chordee. Of these patients, 41 had severe hypospadias, 9 had epispadias, and 1 had urethral atresia. Graft harvest and placement technique, any resulting complications, and parental satisfaction with cosmetic and functional results were all evaluated. RESULTS: The dermal grafts were harvested from the hairless skin of the inguinal area, using one of two techniques. All were used to fill a tunical defect created by incising the tunica at the point of maximal penile curvature. No complications or postoperative hospitalizations resulted from any of the orthoplasty procedures. At a mean follow-up of 27 months, all patients had excellent cosmetic and functional results. CONCLUSIONS: In patients with significant residual chordee, a dermal graft is our preferred method of penile orthoplasty. This technique provides a straight phallus with a very minimal complication rate, it can easily and successfully be performed as an outpatient procedure, and it has assured an excellent cosmetic and functional result.

Ambulatory Surgical Procedures

Isolated ureteral injury caused by blunt trauma.

OBJECTIVES: Ureteral injury is rare after blunt trauma. Herein is presented this unusual scenario of ureteral trauma in addition to the pathophysiology of this injury. METHODS: A 12-year-old boy sustained a rupture of the right ureter 6 cm below the ureteropelvic junction after a car accident. No other injuries or fractures were identified. RESULTS: Ureteral injury was immediately diagnosed and repaired primarily. Intravenous urography performed 8 weeks after surgery revealed normal ureteral healing without stricture formation. CONCLUSIONS: To our knowledge, the isolated avulsion of the ureter in this location has not been reported previously, but must be considered in those patients with severe blunt trauma and hyperextension injuries.

Accidents, Traffic

The natural history of nephrocalcinosis in premature infants treated with loop diuretics.

PURPOSE: We investigated the natural history of nephrocalcinosis in premature infants treated with furosemide and attempted to identify factors to predict infants most at risk. MATERIALS AND METHODS: We evaluated 13 preterm infants in this longitudinal pilot study. During hospitalization and while receiving a loop diuretic nephrocalcinosis developed in each patient. Patients were divided into groups based on resolution (6) and nonresolution (7) according to spontaneous resolution of nephrocalcinosis at any point during followup. The 2 groups were compared to each other and to a control group. RESULTS: Mean followup after discontinuation of furosemide in the resolution versus nonresolution groups was 10.3 and 7.7 months, respectively. Between the 2 groups there was no significant difference in average gestational age, birth weight, number of days hospitalized or on furosemide, or total furosemide dose. Mean calcium-to-creatinine ratio while receiving furosemide at the time nephrocalcinosis developed was 0.38 in the resolution group but 2.23 in the nonresolution group (p < 0.005). Initial calcium-to-creatinine ratio in age matched infants who did not have nephrocalcinosis was 0.4. Frank renal stones developed in 2 of the 7 patients without resolution and 0 of the 6 with resolution. When nephrocalcinosis resolved, it was at a mean of 5.2 months following discontinuation of the diuretic. CONCLUSIONS: Early data indicate that nephrocalcinosis resolves in approximately 50% of premature infants 5 to 6 months after discontinuation of furosemide. The only factor that appears to be predictive of the infants who will have resolution is the calcium-to-creatinine ratio when nephrocalcinosis is diagnosed. In patients without resolution this ratio is much higher than in age adjusted normal controls, while in those with resolution it appears normal for age.

Diuretics

The value of Doppler resistive index and peak systolic velocity in the evaluation of porcine renal obstruction.

PURPOSE: We evaluated the use of Doppler resistive indexes and systolic velocities as diagnostic tools in a partially obstructed animal model. MATERIALS AND METHODS: We studied 12 normal pigs by Doppler sonography, which served as control units. In 9 subjects partial ureteral obstruction was then created surgically, and 3 continued as controls. The presence or absence of obstruction was confirmed by ultrasound, antegrade nephrostography and intrapelvic pressure monitoring. Doppler parameters were measured 1 hour to 21 days postoperatively. Resistive index, and angle corrected peak and mean systolic velocities were measured bilaterally from samplings of interlobar and arcuate arteries. An average of 4 samplings per kidney was obtained at each session. Data from the control and obstruction groups were compared for statistical differences. RESULTS: In controls mean resistive index was 0.53, and peak and mean systolic velocities were 0.38 and 0.26 m. per second, respectively. In the subacute period after obstruction (defined as days 4 to 21) mean resistive index was 0.54, and peak and mean systolic velocities were 0.33 and 0.22 m. per second, respectively. Compared to control data there was no significant change in resistive index after obstruction (p = 0.6). However, peak and mean systolic velocities showed significant downward trends (p < 0.05). CONCLUSIONS: Known small sequential changes in renal blood flow after ureteral obstruction are reflected in flow velocities, as measured by duplex Doppler sonography. However, resistive indexes are not useful in assessing these changes in renal blood flow, and they do not correlate with the presence or absence of obstruction in this animal model.

Animals

The use of laparoscopy in the management of the nonpalpable testis.

Fifty-eight children with a nonpalpable testis have been evaluated at our institution between 1988 and 1994. Laparoscopy was performed in these children to effect a treatment plan. The children range in age from 10 months to 14 years. Thirty patients had a nonpalpable left testis, 18 had a nonpalpable right testis, and 10 had bilateral nonpalpable testes. In 28 children, a testis was visualized. Two underwent laparoscopic orchiectomy and 26 underwent either a standard single stage procedure (11), a staged open procedure (3), or a laparoscopically assisted staged procedure (12). Attenuated vessels were seen in 26 patients and inguinal exploration revealed a viable testis in 6 patients and a testis remnant, which was removed, in 20 patients. Four patients had laparoscopic blind-ending vessels. Diagnostic laparoscopy affords the surgeon not only the ability to localize the testis with virtual certainty, but also the advantage of planning a highly successful treatment program. The position of the testis intra-abdominally and the length of the spermatic vessels can be easily evaluated to decide whether a staged approach versus a single stage procedure can be performed. The use of the KTP laser has made the two staged procedure quite easy with only one Trocar site necessary. This experience has allowed us to develop and modify an algorithm for the effective management of the nonpalpable testis.

Adolescent

A paradoxical elevation of brain cyclo(His-Pro) levels in hyperphagic obese Zucker rats.

Several studies suggest a role for endogenous cyclo(His-Pro) or CHP in appetite regulation. In the present study, we have examined the regional brain distribution of CHP in hyperphagic obese Zucker rats and their lean littermates. The data show a significant elevation in the levels of CHP in many brain regions, including hypothalamus of the obese rat. Within the hypothalamus, the lateral hypothalamic (LH) nucleus of obese rats had significantly higher levels of CHP when compared to that of the lean littermates. Administration of dehydroepiandrosterone, a steroid hormone known to decrease food intake and body weight gain, to obese rats led to decrease in the levels of CHP in the LH. These data further suggest a role for the endogenous CHP in attenuating food intake.

Animals

Cardiorespiratory changes in children during laparoscopy.

The authors prospectively examined the cardiorespiratory changes during brief laparoscopy (less than 15 minutes) in children. Intraoperative ventilatory management included a tidal volume of 12 mL/kg, with the rate adjusted to achieve an end-tidal CO2 (PETCO2) of 30 to 35 mm Hg. The initial rate and tidal volume were not changed during the procedure. Baseline measurements of heart rate, blood pressure, peak inflating pressure (PIP), PETCO2, and oxygen saturation were recorded every minute for 5 minutes before the start of the laparoscopic procedure, and every minute during the laparoscopic procedure. Fifty-five patients were enrolled in the study (age range, 1 month to 7 years; weight range, 5.2 to 31 kg). PIP increased from the baseline value of 20 +/- 2.5 to 23 +/- 3.2 cm H2O (P < .01) during laparoscopy. The increase in PIP was 5 or more in six patients, with a maximum of 7. PETCO2 increased from the baseline value of 32 +/- 3.1 to 35 +/- 4.8 mm Hg (P < .01). The PETCO2 returned to baseline within 10 minutes after completion of the laparoscopy. No increase in ventilatory parameters was required during the brief laparoscopic procedure.

Blood Pressure

REM sleep deprivation alters dopamine D2 receptor binding in the rat frontal cortex.

REM sleep deprivation (RSD) of rats results in facilitation of dopaminergic behavior and an increase in striatal D2 receptor density. To determine whether RSD results in changes in D2 receptor in other brain regions, receptor affinity (Kd) and density (Bmax) were measured in the anteromediofrontal (AM), cingulate (CN), and sulcal cortex (SL) in four groups of rats: 1), RSD96 group (RSD for 96 h; small pedestal/water tank method), 2) RSD24 group (large pedestals for 72 h then small pedestals for 24 h), 3) tank control group (TC; large pedestals for 96 h), and 4) cage control group. In separate groups, ambulation was recorded for 30 min following treatments. Group RSD96 showed an increase in activity compared to TC, and TC was increased compared to CC (p < 0.05 for all). In group RSD24, the AM showed an increase in Bmax and Kd (p < 0.05), but there were no effects by RSD96. In the CN, Bmax and Kd were decreased by RSD96 (p < 0.05) but not RSD24. In the SL, Bmax was increased by RSD96, but not RSD24, whereas Kd was increased in both RSD groups (p < 0.05).

Animals

Congenital hemangiopericytoma of the clitoris.

Hemangiopericytoma is a rare vascular tumor that is believed to arise from the pericyte of Zimmermann. Approximately 10% of cases occur in children and a third are congenital. To our knowledge we report the first case of a congenital hemangiopericytoma arising from the clitoris, describe its management and review the literature.

Clitoris