The Risk of Myocardial Infarction Associated with Antihypertensive Drug Treatment in Persons with Uncomplicated Essential Hypertension

We conducted a case-control study based on computer-recorded information accrued in the United Kingdom General Practice Research Database to assess and compare the relation between different antihypertensive drug therapies and myocardial infarction in patients with no known clinical or laboratory risk factors for myocardial infarction other than hypertension. Cases were treated hypertensive patients with no other known risk factors who developed a first acute myocardial infarction between January 1, 1993, and October 31, 1994. They were ascertained from a review of the clinical record together with a questionnaire filled out by the attending general practitioner. Controls were matched to each case for age, sex, general practice, and index date. Antihypertensive therapy was derived from the computerized patient record. The study consisted of 210 cases and 793 controls. Compared with users of β-blockers alone, the adjusted relative risk (RR) estimates for all other treatment regimens were close to 1.0. A comparison of users of calcium channel blockers alone with users of β-blockers alone yielded a RR estimate of 0.9 (95% CI 0.5, 1.7). We conclude that the risk of acute myocardial infarction in otherwise healthy, treated hypertensive patients is not materially associated with the particular drug they receive.     

dCTP misincorporation in a Chinese hamster mutator phenotype: the role of GGA genetic context

Clone CSA7 is a CHEF18 hamster cell line that shows an increasedintracellular accumulation of dCTP. To localize the mutationsthat accumulate spontaneously in a functional gene of such amutator phenotype, independent CSA7 mutants of the hypoxanthine–guaninephosphoribosyl transferase (hprt) gene were isolated and screenedby a polymerase chain reaction–single strand conformationpolymorphism technique. Sixty-two percent of mutants produceddetectable changes of the strand migration profile and the mutationswere preferentially localized in the exons 3 (31%) and 6 (62%).The sequencing of such exons revealed that the rate of C baseincorporation was the major mutation pathway and that the Abase of a GGA sequence was the preferential site of misincorporation. ³To whom correspondence should be addressed     

Desensitization of AMPA Receptors Limits the Amplitude of EPSPs and the Excitability of Motoneurons of the Rat Isolated Spinal Cord

Intracellular recording was used to study the effect of cyclothiazide, a selective blocker of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on lumbar motoneurons of the rat isolated spinal cord. Cyclothiazide (25 μM) enhanced the responses to AMPA in a tetrodotoxin-insensitive fashion, without affecting those produced by N -methyl-D-aspartate or γ-aminobutyric acid. Excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation were strongly potentiated in amplitude while paired-pulse depression (produced by applying pairs of pulses at 2 s interval) of the EPSP was decreased. In the presence of cyclothiazide the frequency of spontaneous synaptic events was greatly increased and network-driven bursting activity developed with eventual loss of electrical excitability. The present results suggest that pharmacological block of AMPA receptor desensitization led to strong excitation of motoneurons and indicate a physiological role of desensitization in protecting these nerve cells from overactivity.     

An evaluation of Tourette Syndrome and medication use in Canada

Self-report data were gathered from a national sample of over 200 Canadian Tourette Syndrome (TS) patients. Information regarding symptom severity both on and off medication was gathered along with an analysis of different medications in use, and patient ratings of effectiveness of those medications. Patients also rated their own mental health. Results indicated that approximately 60% of TS patients take some form of medication for relief from their symptoms. Of these, over 80% reported that symptoms are less severe when medicated. The most commonly prescribed medications in order of popularity are haloperidol, pimozide, clonidine and benztropine mesylate (Cogentin). Patient ratings of effectiveness of these medications places haloperidol first, pimozide second and clonidine third although all were found to be "somewhat" to "very" effective. Of those TS patients on medications, 50% rated their own mental health as good to excellent and 50% rated it as fair to poor.     

Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men

Nocturnal penile tumescence (NPT) studies were evaluated in 17 men with a clinical diagnosis of organic erectile dysfunction in comparison to age-matched healthy controls (n = 17) and depressed men (n = 17). The dysfunctional group had significantly fewer NPT episodes and reduced maximal penile tip changes when compared to healthy controls and depressed patients. Further, the dysfunctional group had significantly diminished erectile fullness and reduced penile rigidity. Diagnostic performance of polygraphic (night 1) and visual inspection (nights 2 or 3) components of the NPT protocol were examined in these criterion groups. A diagnostic classification based on polygraphic measures successfully discriminated 73.5% of dysfunctional and healthy control subjects, but classified 47% of depressives in the dysfunctional range. Use of visual inspection indices correctly identified 88% of the dysfunctional sample and 94% of normal controls, and reduced the "false-positive" rate in depression to only 18%. Results support the diagnostic utility of NPT studies, particularly when enhanced by visual inspection procedures. Nevertheless, the presence of major depression may confound interpretation of such studies.     

Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity.

We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.     

The potential role of lonidamine (LND) in the treatment of malignant glioma

Summary Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with unconventional modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.