The "blockade" of Cuba: setting the record straight.
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Biomedical subjects
Publications and source records attributed to E Perez-Stable.
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That CYP2D6 activity is an important determinant of nicotine metabolism and that people who have abnormal CYP2D6 genes are poor metabolizers of nicotine has been reported in the medical literature. The aim of this study was to assess the role of CYP2D6 in nicotine metabolism. Specifically, we compared the clearance of stable isotope-labelled nicotine and cotinine in 11 poor and 33 extensive metabolizers of dextromethorphan, a probe for CYP2D6 activity. The groups were matched by gender, age and ethnicity. Nicotine and cotinine kinetics were quite similar for cases and controls. These data suggest that CYP2D6 is not a major isozyme for the metabolism of nicotine or cotinine.
We studied the clinical and pathological data for 334 patients age 65 or more who underwent renal biopsy for acute renal failure (ARF, n = 55), subacute renal failure (SRF, n = 72), chronic renal failure (CRF, n = 57), proteinuria (n = 137), and hematuria (n = 13). Tissue diagnoses were glomerulopathy (n = 252, 75.4%), acute tubular lesions (n = 18), interstitial nephritis (n = 23), vascular diseases (n = 36, including 14 with cholesterol emboli), and five miscellaneous diagnoses. Of the 55 patients with ARF, 23 had a glomerular lesion, 15 had acute tubular necrosis, and 8 had acute interstitial nephritis. Of 72 patients with SRF, 49 had a glomerulopathy, 12 had a vascular disorder, and six had acute interstitial nephritis. Hence, patients with ARF or SRF exhibited a high potential for reversible lesions. Only 11.3% of patients with CRF had potentially reversible causes. The most common causes of proteinuria were membranous glomerulopathy (34.3%), minimal change disease (14.6%), focal segmental sclerosis (11.7%), and amyloidosis (8.8%). Of the 25 patients with advanced nephrosclerosis, 24 had renal failure, 20 were hypertensive, and 13 had cholesterol emboli. Of 33 patients with diabetes mellitus, 66.7% were found to have lesions not related to diabetes. We conclude that renal biopsy is most useful in older patients with ARF or SRF because of potentially reversible renal disease. Old age alone is not a contraindication to performing a renal biopsy.
Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.
Investigation of coronary heart disease manifesting as sudden death has highlighted the role of electrolyte disturbances in arrhythmogenesis. The identification of the 3 major cardiac risk factors--hyperlipidaemia, hypertension and smoking--does not fully explain sudden death in asymptomatic patients with an abnormal ECG. Sudden death is usually ascribed to cardiac arrhythmia whose pathogenesis has 3 possible mechanisms affecting the electrical properties of the heart. Thiazide diuretics are known to deplete potassium and magnesium in the body and while magnesium deficiency has been especially associated with cardiac rhythmicity, potassium levels modulate the cellular effects of calcium in the myocardium. In patients with ischaemic heart disease, both hypokalaemia and hypomagnesaemia correlate with the frequency of serious arrhythmias and even in ambulatory hypertensive patients on diuretics, it is important to preserve electrolyte homeostasis. There is, however evidence to suggest that some patients are more susceptible to diuretic-induced arrhythmias and in these patients even mild hypokalaemia can cause ventricular arrhythmias, and age may be a contributory factor. The risk of thiazide-induced arrhythmias has yet to be confirmed.
We studied 17 hypertensive men to determine the relationship of diuretic-induced hypokalemia to ventricular ectopic activity ( VEA ). Blood values and 24-hour ambulatory ECG monitoring were done at baseline, after diuretic and after serum potassium normalization. Two subgroups of patients were identified: group A patients were older (63.0 vs. 53.8 years) and had clinical evidence of organic heart disease compared to group B. Group A had increased frequency and complexity of VEA with diuretic which reverted to baseline after potassium normalization. Group B had no changes. Serum and intra-red blood cell potassium decrements were equal in both groups. We conclude that clinical in addition to laboratory observation should be used to identify those hypertensive patients most susceptible to diuretic-induced VEA and their serum potassium level should be normalized in order to minimize this complication.
Long-term thiazide diuretic therapy for hypertension is associated with disturbances in carbohydrate, lipid, and potassium metabolism that theoretically may have serious adverse effects. It appears that diuretic-induced hypokalemia interferes with production of insulin, producing mild elevations of blood glucose in nondiabetic patients. The insulinopenia worsens glucose metabolism in prediabetic and type II diabetic patients. Increases in low-density lipoprotein cholesterol, triglycerides, and the low-density lipoprotein/high-density lipoprotein cholesterol ratio are frequently seen following thiazide treatment of hypertension. These changes are more pronounced in younger patients. Decrements of serum potassium of 0.6 mEq/L are commonly observed with diuretic therapy. Usually, patients remain asymptomatic and no potassium replacement is necessary. In patients with underlying heart disease, however, alterations in potassium metabolism may produce increased frequency and complexity of ventricular ectopic activity. All these metabolic disturbances appear to be, in part, dose related, and there is currently no evidence that they have clinical significance.
The mean minimal and average basal lamina thickness (MBLT and ABLT) of 17 to 20 muscle capillaries were measured in 26 overt juvenile diabetics and in 26 nondiabetic patients of similar age. The mean MBLT was significantly increased in diabetics although 17 of the individual values in diabetics overlapped those obtained in nondiabetics. Segmental and focal fluctuations in basement membrane width appeared to be the most important cause of variance, particularly in thick walled vessels, although multiple instrumental and technical sources of error were also present. As a result, in diabetics there was a mean variability of +/-25% when measurements from two different sets of capillaries in the same subject were compared. Patients older than 12 years and diabetics with longer duration of the disease or abnormal findings on ophthalmoscopic examination exhibited a significant increase in capillary basal lamina. The mean ABLT averaged 1.8 times the mean MBLT, but the relative individual measurements as well as statistical correlations with clinical parameters were similar. Muscle capillary basement membrane hypertrophy, as quantitated by the present methods, does not seem to be an early, sensitive or consistent finding to identify individual diabetics.
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