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K Frey

Publications and source records attributed to K Frey.

At least 37 records · Page 2Linked to original sources
PubMed1995

The vesicular monoamine transporter is not regulated by dopaminergic drug treatments.

The number of neuronal synaptic vesicular monoamine transporters (vesicular monoamine transporter type 2; VMAT2) has been recently proposed as an index of monoamine presynaptic terminal density. The present study investigated the possible regulation of the vesicular monoamine transporter. Rats were treated for 2 weeks with drugs known to influence dopaminergic neurotransmission, including those commonly used in the treatment of Parkinson's disease. Autoradiographic assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN 35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma membrane dopamine re-uptake site bindings, respectively. None of the drug treatments significantly modified levels of vesicular monoamine transporter binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites were altered by some of the treatment regimens. These data extend preliminary results that suggest the vesicular monoamine transporter is not easily regulated and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake site. Measures of striatal vesicular monoamine transporter density may, thus, provide objective estimates of monoaminergic innervation in neurodegenerative diseases, unaffected by the use of symptomatic therapies.

Animals↗
PubMed1995

Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific.

The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3 microM). Each isomer was then synthesized in carbon-11 labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-alpha-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.

Animals↗
PubMed1994

The stress response to laparoscopic cholecystectomy: investigation of endocrine parameters.

Laparoscopic cholecystectomy, as a typical example of minimal invasive surgery, is associated with low complication rates and minimal patient discomfort, and provides the same safety as conventional cholecystectomy. In the present prospective observational study, endocrine parameters as indicators for stress response were measured. We investigated 53 patient with laparoscopy cholecystectomy and 12 patients with conventional cholecystectomy. Blood samples were taken pre-, peri-, and postoperatively for measurement of ACTH, cortisol, prolactin, and growth hormone. General anesthesia followed a standardized protocol. The increase in all stress hormones did not differ between patients in the two groups, and was comparable with that reported in the literature and the findings of our own previous studies in patients undergoing conventional cholecystectomy and elective colon resection. We conclude that laparoscopic cholecystectomy is associated with a pronounced endocrine stress response that does not account for the observed differences in the peri- and postoperative complication rate or patient comfort.

Adrenocorticotropic Hormone↗
PubMed1993

Chronic electrical stimulation reverses deafness-related depression of electrically evoked 2-deoxyglucose activity in the guinea pig inferior colliculus.

The [14C]-2-deoxyglucose (2-DG) autoradiographic technique was used to study how auditory-related metabolic activity changes with deafness, and how chronic electrical stimulation of the deafened system may modify these changes. Guinea pigs were deafened by administration of kanamycin and ethacrynic acid. After nine weeks of deafness, the basal unstimulated uptake of 2-DG in the inferior colliculus (IC) was lower than in normal hearing control animals. 100 microA of acute cochlear electrical stimulation significantly increased 2-DG uptake in normal hearing animals but did not evoke a significant increase in four or nine week deafened animals. Electrically elicited 2-DG uptake in the IC is therefore depressed by prolonged deafness. In a second series of experiments, after four weeks of deafness, animals were chronically electrically stimulated via a cochlear implant 2.5-3.5 h a day, five days a week for five weeks at 100 microA. Acute cochlear electrical stimulation following this chronic stimulation significantly increased 2-DG uptake in the contralateral IC over unstimulated levels. This suggests that some depressive effects of profound deafness on the auditory brain stem may be reduced or reversed with chronic electrical stimulation by a cochlear implant.

Animals↗
PubMed1989

Pelvic exenteration in clear cell adenocarcinoma of the vagina and cervix.

Pelvic exenteration was performed in 29 of 527 cases of vaginal and cervical clear cell adenocarcinoma (CCA). Exenteration was the initial therapy in 21 cases (1 stage I, 15 stage II, 3 stage III, 1 stage IV, and 1 unknown stage) and was undertaken in 8 cases for central failure after primary radiotherapy. Of the 78 patients with stage II vaginal CCA, the 9 treated with primary exenteration were compared with the 69 who had other modalities of therapy; no significant difference in the survival experience was noted between the two groups. Among the 96 patients with stage II cervical CCA the survival experience was less favorable for those who underwent primary exenteration (n = 5) than for those who were treated with other varieties of therapy (n = 91). Of the 34 patients with central treatment failure, 8 had exenteration and 26 had other forms of therapy. The overall 5- and 8-year actuarial survival rates for the exenteration group (100 and 60%) do not differ significantly from those for the nonexenteration group (71 and 56%). Primary exenteration was used more frequently in the 1970s but has been predominantly reserved for the treatment of recurrent disease during the past decade. Survival statistics after exenteration for central failure are more favorable in cases of vaginal and cervical CCA than in cases of cervical squamous carcinoma.

Adenocarcinoma↗
PubMed1988

Infertility among daughters either exposed or not exposed to diethylstilbestrol.

Infertility was examined among 343 diethylstilbestrol-exposed and 303 unexposed daughters whose mothers participated in an evaluation of diethylstilbestrol use during pregnancy 35 years ago. Of the married individuals who were not using contraception and who were actively trying to conceive, a greater proportion of diethylstilbestrol-exposed women than unexposed subjects experienced primary infertility (33% versus 14%, p less than 0.001). Among those with primary infertility, abnormal hysterosalpingograms were observed in 46% of the diethylstilbestrol-exposed group and in none of the unexposed group (p less than 0.02), while tubal abnormalities were found in 42% of the exposed and in none of the unexposed (p = 0.02). First pregnancies were achieved by 40 (58%) women exposed to diethylstilbestrol and 18 (64%) unexposed subjects. Twenty-four (60%) of the exposed women and 15 (83%) of the unexposed individuals who conceived had a live-born infant who survived. The estimated cumulative rate of first pregnancy was 16% for the exposed group and 36% for the unexposed group at 12 months after the diagnosis of primary infertility (p less than 0.05).

Adult↗
PubMed1975

[Bartter's syndrome and tubular functional disturbances].

A 5-year-old boy is presented who exhibited the classical symptoms of the syndrome described by BARTTER et al. in 1962: growth retardation, hypokalemic alkalosis, hyperplasia of the juxtaglomerular apparatus with normotensive hyperreninism-hyperaldosteronism, polydipsia with impaired renal concentration ability resistant to pitressin. In addition, the patient showed the typical proximal tubular defects of the Fanconi syndrome: hyperphosphaturia with hypophosphatemic ricktts, generalized hyperaminoaciduria, proteinuria and glucosuria. In the cases of Bartter's syndrome described to date, no uniform pathogenetic mechanism could be identified. Proximal tubular salt wasting generally is assumed to be the primary defect. The studies carried out in this case support this hypothesis and indicate that the complete clinical picture of Bartter's syndrome may occur within the framework of multiple proximal tubular defects.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Sympathetic block during spinal anesthesia in volunteers using lidocaine, tetracaine, and bupivacaine.

BACKGROUND AND OBJECTIVES: Spinal anesthesia to high thoracic dermatomes is alleged to result in almost complete block of all sympathetic efferent nerves. To examine the degree of sympathectomy during spinal anesthesia, the sympathetic response to a cold pressor test (CPT) applied to unblocked dermatomes before and during spinal anesthesia was measured with use of three different local anesthetics. METHODS: Twelve healthy volunteers were studied in a randomized and double-blind fashion on three separate occasions. In random order, each volunteer received approximately equipotent spinal doses of tetracaine 15 mg, bupivacaine 15 mg, and lidocaine 100 mg in hyperbaric solutions. Prior to and 30 minutes after spinal injection of local anesthetic, a CPT was applied for 2 minutes, and changes from baseline resting conditions in five physiologic variables were measured. RESULTS: The CPT 1 given before anesthetic administration resulted in an increase in heart rate, mean arterial pressure, cardiac index, and plasma concentrations of norepinephrine and epinephrine. Spinal anesthesia to a median level of T3 resulted in a decrease in mean arterial pressure by 10-12% but did not significantly decrease the other variables. Spinal anesthesia did not change the increase in heart rate or cardiac index in response to the second CPT, but the increase in mean arterial pressure was attenuated compared to the CPT before anesthesia. No increase in norepinephrine or epinephrine concentration was observed during the CPT given during spinal anesthesia. There was no significant relationship between level of analgesia and sympathetic response to stress. CONCLUSIONS: Spinal anesthesia with hyperbaric solutions of tetracaine 15 mg, bupivacaine 15 mg, and lidocaine 100 mg attenuated sympathetic function but did not produce complete sympathectomy. The effects were independent of the local anesthetic used.

Adult↗
PubMedDate not supplied

Time course of the effects of cervical epidural anesthesia on pulmonary function.

BACKGROUND AND OBJECTIVES: During cervical epidural anesthesia the C4, C5, and sometimes C3 nerve roots are anesthetized. One might therefore expect pulmonary compromise due to the block of the phrenic nerve if anesthesia extends to C3. This study was conducted to measure the effects of cervical epidural anesthesia using 2% lidocaine on pulmonary function, with specific attention given to the time course of pulmonary changes in relation to spread of analgesia. METHODS: Fifteen adult patients without preexisting lung disease undergoing carotid endarterectomy, breast surgery, or cervical epidural steroid injection were enrolled. Cervical epidural anesthesia was performed at the C7-T1 interspace using 300 mg lidocaine with epinephrine. Pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximum inspiratory pressure (MIP), and SpO2 while breathing room air were measured prior to and 5, 10, 20, and 40 minutes after lidocaine injection. RESULTS: Analgesia to pinprick reached median dermatomes of C3 to T8 (range: C2-T12) by 20 minutes after lidocaine injection. FEV1 and FVC decreased approximately 12-16% between 20 and 40 minutes after injection. Maximum inspiratory pressure and SpO2 did not significantly change. CONCLUSIONS: Cervical epidural anesthesia using 300 mg lidocaine results in measurable reduction in bedside pulmonary functions concomitant with the spread of analgesia to the C3 dermatome. These changes were complete 20 minutes after lidocaine injection. In patients without preexisting lung disease, these changes were not clinically significant, except in one patient. We conclude that motor block of the phrenic nerve is incomplete under the conditions of this study.

Adult↗
PubMedDate not supplied

Influence of diuresis on enzymuria.

Urinary excretion of renal brush border enzymes may serve as an early marker of renal injury. However, the distinction between physiological and pathological levels remains controversial, since enzymuria is affected by physiological parameters. To clarify the influence of diuresis, we investigated the urinary excretion of alanine-aminopeptidase (AAP; EC 3.4.11.2) as function of diuretic state. 17 healthy volunteers of both sexes were subjected to protocols with sudden or prolonged water load preceded and followed by a thirst period. Urinary excretion of AAP was measured using an enzyme kinetic assay. As expected AAP excretion increased with urine flow, the increments diminished yielding an overall excretion pattern that resembled saturation kinetics. This function is described by a mathematical model. This model assumes, that AAP is released in proximal tubules at a constant rate and reabsorbed or inactivated in the distal tubule and collecting duct. Non-linear fits of the model equation to our data allowed two parameters, chi and mu, to be defined. Chi describes the rate of AAP release independent of urinary flow, and mu the ratio of distal tubular reabsorption or inactivation. If a substrate is not reabsorbed at all, mu approximates zero. Since mu fitted for AAP differed significantly from zero, this indicates reabsorption or inactivation of AAP in the distal nephron. Therefore, our study supports the theory of flow-dependent reabsorption or inactivation of AAP in the distal nephron.

Adult↗