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Biomedical subjects

R Kroll

Publications and source records attributed to R Kroll.

13 recordsLinked to original sources
PubMed2000

Stuttering: an update for physicians.

Stuttering is a disturbance in the normal fluency and time patterning of speech. Developmental stuttering (DS), with or without associated psychiatric illness, is the most common form and includes all cases with gradual onset in childhood that are not the result of acquired brain damage. Persistent developmental stuttering (PDS) is DS that has not undergone spontaneous or speech-therapy-induced remission. Organic models of DS focus on incomplete lateralization or abnormal cerebral dominance. There is also evidence that DS has a significant genetic component to its cause. Neuroimaging research data and the effectiveness of dopamine receptor antagonists in DS seem to support the theory of a hyperdopaminergic origin. Speech therapy remains the main treatment for DS; however, antidepressants can be useful in selected cases. Risperidone, a serotonin-dopamine antagonist, has been shown to be more effective than placebo in decreasing the severity of stuttering. The long-term efficacy and safety of serotonin-dopamine antagonists in DS deserve further study.

Adult↗
PubMed2000

Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia - updated results of the multicentre study of 378 patients.

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

2-Chloroadenosine↗
PubMed1998

Technique of, and complications attributable to, repeated hyperosmotic blood-brain barrier disruption in dogs.

OBJECTIVE: To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD. ANIMALS: 10 healthy adult dogs. PROCEDURE: Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens. RESULTS: Seven dogs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation. CONCLUSION: Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs. CLINICAL RELEVANCE: Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.

Animals↗
PubMed1988

The possible role of the ethanol-inducible isozyme of cytochrome P450 in the metabolism and distribution of carbon disulfide.

Acute treatment with ethanol and other alcohols has been shown to potentiate the hepatotoxicity of certain xenobiotics, in part via induction of the mixed-function oxidase (MFO) system. Carbon disulfide (CS2)-induced hepatotoxicity and inhibition of the MFO system have been shown to be a consequence of MFO metabolism. In the present study, the ability of several different alcohols to induce the hepatic MFO metabolism of CS2 and the effects of this induction on CS2 distribution and hepatotoxicity were examined in rats. Eighteen hours after alcohol administration (1/2 LD50 dose, po), CS2 microsomal MFO metabolism was significantly enhanced, in order of descending potency, by isopropanol, methanol, and ethanol pretreatments, but not by isobutanol pretreatment. The degree of enhancement of CS2 metabolism by different alcohols paralleled the enhancement of nitroanisole O-demethylation and aniline hydroxylation, MFO activities associated with the ethanol-inducible isozyme of cytochrome P450. CS2 (1 mg/kg, ip, 3 hr) inhibited only the cytochrome P450-mediated activities enhanced by alcohol pretreatment. These results suggest that CS2 metabolism is catalyzed by the ethanol-inducible isozyme. Alcohol-induced rats had significantly more 14CS2-derived radioactivity in the liver than control and isobutanol-pretreated rats 3 hr after dosing (1 mg/kg, ip). However, only methanol pretreatment resulted in an increased retention of 14CS2-derived radioactivity in plasma, brain, and kidney. Unlike other alcohol pretreatments, methanol decreased the total 14C expired during the 3-hr period after CS2 dosing and caused a significant (twofold) increase in plasma glutamic-pyruvic transaminase, measured 24 hr after CS2 exposure (625 mg/kg). These data indicate that alcohol induction of MFO-dependent CS2 metabolism per se is not sufficient to result in CS2-induced hepatic damage although it does lead to loss of specific cytochrome P450 function.

Alanine Transaminase↗
PubMed1982

Assessment of the mutagenicity of phthalate esters.

The Ames assay was used to investigate the mutagenicity of several phthalate esters as an approximation of their carcinogenic potential. The ortho diesters, dimethyl phthalate (DMP) and diethyl phthalate (DEP) produced a positive dose-related mutagenic response with Salmonella TA100, but only in the absence of S-9 liver enzymes. Dibutyl, di(2-ethylhexyl), mono(2-ethylhexyl), and butyl benzyl phthalate as well as the dimethyl isophthalate and terephthalates and the trimethyl ester, trimellitate, were not mutagenic with TA100 or TA98 in the presence or absence of S-9. In a host-mediated assay, extracts of 24-hr urines of rats injected IP with DMP (2 g/kg) were not mutagenic to TA100 at levels up to 8 equivalent-ml of urine/plate (representing 30% of their daily urinary output). In vitro studies revealed that S-9 associated esterase hydrolyzed DMP to the monoester and methanol and eliminated its mutagenicity. Whole rat skin was shown to have about 1.5% of the DMP-esterase activity of liver, when compared on a wet weight basis. An in vitro binding study indicated that epidermal macromolecules bound DMP at a severalfold greater rate than hepatic macromolecules. Thus, both the mutagenicity and binding of DMP are inversely related to the metabolism of this compound. These results suggest that skin could be at high risk for a mutagenic/carcinogenic insult.

Animals↗
PubMed1977

Superselective transcatheter embolization of traumatic renal hemorrhage.

Selective angiography is an established diagnostic modality in acute renal trauma [1-3]. Renal hemorrhage, once demonstrated by angiography, can then be treated by arterial embolization [4-5]. This paper describes the successful transcatheter management of a renal laceration in a patient with multiple injuries secondary to an abdominal gunshot wound. Adominal exploration had established that the renal hemorrhage could not be surgically controlled without performing a nephrectomy.

Adult↗
PubMedDate not supplied

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.

Adaptation, Psychological↗
PubMedDate not supplied

Seven-year follow-up of speech/language-impaired and control children: speech/language stability and outcome.

OBJECTIVE: This study examined the 7-year outcome of speech/language (S/L) impaired and control children selected from a community sample at age 5 years. METHOD: Two hundred fifteen children completed a variety of speech and language tests at age 12 years. Children with S/L impairment were further classified as "speech only," "language only," or "speech and language impaired." RESULTS: More than 72% of children who had S/L impairment at age 5 remained impaired at age 12. Children with both speech and language problems were most likely to remain S/L impaired; 81% had some kind of S/L impairment at follow-up. Similarly, children with both expressive and receptive language impairment were more likely to show expressive or receptive impairment at follow-up than children with expressive impairment alone. One third of time 1 controls had S/L problems at follow-up, and of these 82% had speech impairment only. CONCLUSIONS: S/L impairment identified at age 5 has long-lasting effects. More pervasive problems were associated with poorer outcomes. Screening at age 5 may be useful, as most serious S/L problems that emerged by middle childhood could be identified at age 5. The effects of S/L treatment require further study.

Adolescent↗