Differential effects of sulindac on renal hemodynamics and function in the rat

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n=6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n=12). In the 5 mg/kg b.w. sulindac group (n=7), renal blood flow progressively and significantly increased from 7.88±0.36 to 8.98±0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n=7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n=5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P<0.025). Also, Na⁺ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n=15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n=21), it was decreased from 11.5±1.2 to 7.4±0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P<0.05; n=6). In conclusion, differential effects of sulindac on renal hemodynamics, Na⁺ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.     

Multiple Cranial Nerve Palsies in a Patient 15 Years after Curative Therapy for a Pituitary Adenoma

Over a 3-year period, a 31-year-old man developed multiple cranial nerve palsies consisting of diplopia, left-sided facial numbness and weakness, and loss of the left corneal reflex. Fifteen years prior to presentation, he had undergone curative therapy for a prolactin-secreting pituitary macroadenoma. The imaging studies were helpful in localizing the disease process, which correlated well with the clinical examination, and for focusing the differential diagnosis.     

A glutamatergic mechanism for aluminum toxicity in astrocytes

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.     

Phase I/II trial of dipyridamole, 5-fluorouracil,leukovorin, and mitoxantrone in metastatic breast cancer

Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m² by mouth every 6 h (700 mg/m²/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m² was given intravenously immediately prior to 5-FU 375 mg/ m² intravenously on days 1–5. Mitoxantrone 6 mg/m² was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m² days 1–2, 5-FU 375 mg/m² days 1–2, mitoxantrone 6 mg/m² on day 2, and dipyridamole 175 mg/m² every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.     

Choroid plexus cysts-Association with trisomy: Prospective review of 16,059 patients

OBJECTIVE: The purpose of the study was to determine the incidence of isolated choroid plexus cysts in association with trisomy 18 and other abnormalities.STUDY DESIGN: All patients from June 1992 through December 1995 were followed up after a screening ultrasonography. Any patient with a choroid plexus cyst was offered genetic counseling and an amniocentesis. Screening ultrasonographic examinations were performed on 16,059 patients, and 301 patients had a fetus with a choroid plexus cyst. One hundred thirty patients elected to have an amniocentesis. Patients were followed up to delivery.RESULTS: Two hundred sixty-three patients had an isolated choroid plexus cyst. Thirty-eight patients had a choroid plexus cyst associated with additional risk factors. Risk factors included advanced maternal age, additional ultrasonographic abnormalities, past obstetric history, or family history. No abnormalities were noted in the group with an isolated choroid plexus cyst. Four patients had an abnormality when the choroid plexus cyst was associated with an additional risk factor, including two patients with trisomy 18 and one with trisomy 21.CONCLUSION: An isolated choroid plexus cyst was not associated with a trisomy or other abnormalities in this study. When a choroid plexus cyst was associated with an additional risk factor, 10.5% of the patients had an abnormality. Amniocentesis is recommended when a choroid plexus cyst is found in association with additional risk factors. (Am J Obstet Gynecol 1997;176:1381-3.)     

Ocular Pharmacokinetics and Pharmacodynamics of Phenylephrine and Phenylephrine Oxazolidine in Rabbit Eyes

The aqueous humor concentration of phenylephrine and its corresponding mydriatic response were measured over time in New Zealand albino rabbit eyes following a 10-µl topical instillation of a phenylephrine HC1 viscous solution (10%) or a phenylephrine oxazolidine (prodrug) suspension in sesame oil (1 and 10%). The bioavailability of a 1% prodrug suspension in the rabbit eye (AUC of aqueous humor concentration vs time) was 30% lower than that of a 10% phenylephrine solution (P < 0.1) with the exception that the peak time occurred 34 min earlier with the prodrug. A 10% prodrug suspension increased the aqueous humor bioavailability approximately eightfold but improved the mydriatic activity (AUC of mydriasis vs time) only fourfold. The pharmacokinetic parameters, apparent absorption, and elimination rate constants, of phenylephrine and the prodrug were determined from aqueous humor concentration–time and mydriasis–time profiles. The study showed that the kinetic parameters of phenylephrine estimated from its mydriasis profile do not accurately reflect the kinetics of drug distribution in the iris. These parameters also varied with the instillation of phenylephrine solution or prodrug suspensions. A mydriatic tolerance of the pupil response was apparent after the topical instillation of phenylephrine solution. The mydriatic tolerance may be due to the decrease in receptor number in the iris dilator muscle.     

Evaluation by dental students of a communication skills course using professional role-players in a UK school of dentistry

This paper reports student (n = 180) feedback on the role-play teaching methodology used in behavioural sciences teaching at The School of Dentistry in Birmingham (UK). The feedback received on this well-established (since 1995) educational programme was collected via questionnaire (100% response rate), requiring Likert scale and free text responses. Generally students reported that they had enjoyed and valued the session. Over two-thirds (69.7%) of students rated the role-players as 'very real' and over three-quarters (78.9%) rated their feedback as 'very fair'. The data collected from this study will inform future curriculum development. Student feedback was very positive and demonstrated that the cohort (86% of all students studying in years 1, 2 and 3) found the use of professional role-players involved in behavioural sciences teaching to be both acceptable and valuable.