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Biomedical subjects

M R Weir

Publications and source records attributed to M R Weir.

At least 163 records · Page 9Linked to original sources
PubMed1990

Depression of vitamin B6 levels due to theophylline.

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.

Administration, Oral↗
PubMed1989

Preliminary observations of the acute effects of selective serum thromboxane inhibition and angiotensin converting enzyme inhibition on blood pressure and renal hemodynamics in hypertensive humans.

CGS 13080, a selective thromboxane synthetase inhibitor, was given intravenously (0.6 mg/kg over 6 hours) to eight hypertensive (diastolic 95-115 mm Hg) euvolemic caucasian females on their customary salt intake (24 hour urine Na: 142.9 +/- 14.8 meq). No change occurred in blood pressure or glomerular filtration rate (GFR): 95.2 +/- 7.2, control versus 95.0 +/- 9.0, CGS 13080 (ml/min); or renal plasma flow (RPF): 363.2 +/- 34.2, control, versus 373.2 +/- 31.2, CGS 13080, (ml/min). Prostaglandin production was altered: platelet generation of thromboxane B2 83.3 +/- 10.9, control, versus 5.4 +/- 1.8, CGS 13080 (ng/hr) (P less than .001); urinary prostaglandin E (PGE) 249.0 +/- 56.3, control, versus 443.9 +/- 79.8, CGS 13080 (ng/6 hr) (P = .06); urinary 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 188.6 +/- 23.4, control, versus 287.9 +/- 21.8, CGS 13080 (ng/6 hr) (P = .01); urinary thromboxane B2 54.8 +/- 12.9, control, versus 58.6 +/- 20.3 CGS 13080 (ng/6 hr) (P = NS). Serum levels of renin, angiotensin II and aldosterone were not altered by CGS 13080. Captopril when dosed to lower diastolic blood pressure 5-7 mm Hg did not significantly affect GFR, RPF or RVR. Nor did it affect platelet generation of thromboxane B2 or urine concentrations of PGE, 6-keto-PGF1 alpha or thromboxane B2. Captopril did increase renin levels 1.2 +/- 0.2, control, versus 2.9 +/- 1.1, captopril (ng/ml/hr) (P = NS), but did not statistically change angiotensin II, or aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Stress reaction of the pars interarticularis leading to spondylolysis. A cause of adolescent low back pain.

We report an adolescent with progression from a stress reaction of the pars interarticularis without radiographic findings, to radiographic fracture and spondylolysis, illustrating the evolution of spondylolysis in an athletically active early adolescent. Gymnastics, diving, pole vaulting, or collision/contact sports such as football, soccer, hockey, and la crosse are common sports with a disproportional frequency of spondylolysis. Rotational forces around the long axis of the spine with load bearing hyperextension are important in etiology. Low back pain in the active adolescent or preadolescent, even with normal oblique lumbar radiographs, may have a treatable origin--stress reaction or fracture of a lumbar pars interarticularis. Screening evaluation is the standing one-leg extension maneuver. Liberal use of nuclear studies for minimal back symptoms in athletic adolescents may help exclude this relatively common, potentially treatable condition, spondylolysis of the pars interarticularis.

Athletic Injuries↗
PubMed1989

Renal allograft biopsy and conversion of cyclosporine to azathioprine.

A prospective nonrandomized study was conducted to evaluate the results of two conversion protocols on two similar groups of renal graft recipients totaling 54 patients who were converted from CsA to AZA at 6-12 months posttransplant. With protocol I, 24 patients (3 haploidentical, 21 cadaveric recipients) were converted with a graft biopsy followed by a 14-day overlap of CsA and AZA before the CsA dose was tapered and discontinued in 6 days. Of the 24 patients, 8 were found to have occult rejection in biopsy and received methylprednisolone 500 mg boluses for three days before overlap started. Thirty patients (2 haploidentical, 28 cadaveric recipients) were converted with protocol II, which had CsA and AZA overlap and tapering schedules identical to those of protocol I without a preconversion biopsy. Follow-up extended as far as 3 years posttransplant. There was a substantial incidence of chronic rejection and graft loss after conversion in protocol II patients. We also found that there was a possible link between postconversion acute rejection and late graft loss from chronic rejection. The incidence of acute rejection after conversion was significantly lower among protocol I patients as compared with that of protocol II (4% vs. 37%, P less than 0.001). However, if 8 patients with occult rejection in the preconversion biopsy were added to the total number of postconversion rejection in protocol I, the incidence of postconversion rejection in this group (38%) would be similar to that of protocol II. Using the time of conversion as the onset of the risk, protocol I patients had better graft survival than protocol II (100% vs. 80%, P less than 0.005) at 3 years posttransplant. If conversion becomes necessary, we recommend a preconversion graft biopsy to identify and treat patients with occult rejection before the beginning of CsA and AZA overlap, especially for those patients whose creatinine is higher than 2 mg/dl without obvious cause before conversion.

Antilymphocyte Serum↗
PubMed1989

Sexual maturity rating: a marker for effects of pubertal maturation on the adolescent electrocardiogram.

The heart is known to participate in the adolescent growth spurt. A peak increase in transverse diameter coincides with peak height velocity during pubertal maturation. The effects of maturation on the adolescent ECG were explored using sexual maturity rating (SMR) as a marker. ECGs were obtained from 751 patients 8 to 20 years of age seen for routine physical examinations. A total of 33 standard ECG measures were analyzed, with subjects separated by sex and SMR. Different trends were seen in boys and girls during the course of maturation for the majority of R and S wave amplitude measurements. Lower mean amplitudes were seen consistently in more mature (SMR 4 and 5) girls than less mature girls and all boys. The clinical implication of these findings is illustrated by analysis of the sum of RV5 and SV2, one of the criteria for left ventricular hypertrophy, by sex and SMR. No significant difference in the sum is noted for boys across five SMR groups. Girls, in contrast, show a steady decrease in the sum with advancing maturation. These trends are not as clearly shown when subjects are grouped by broad chronologic age ranges, as had been the practice in developing current adolescent ECG tables. These findings suggest that development of standard ECG tables in which SMR and sex have been taken into account might enhance interpretation during adolescence.

Adolescent↗
PubMed1988

Pharmacologic management of systemic hypertension in blacks.

This article contrasts the characteristics of essential hypertension found in the black population with that seen in the nonblack population. Socioeconomic and pathophysiologic factors are discussed. Different pharmacologic classes of drugs are compared for their effectiveness in treating the black hypertensive patient. Because black hypertensives tend to have salt-sensitive, low-renin hypertension coupled with decreased cardiac output and high peripheral vascular resistance, an ideal antihypertensive should have natriuretic effects but also the physiologic capability of reducing vascular resistance. Such an ideal hypertensive drug would be able to lower systemic blood pressure while improving organ perfusion and function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Physiologic and hemodynamic considerations in blood pressure control while maintaining organ perfusion.

Essential hypertension remains a significant contributor to mortality, despite treatments effective in decreasing blood pressure. A major reason mortality remains high may be that the conventional stepped-care approach does not always reduce blood pressure in a physiologic manner, which may result in metabolic derangements and elicitation of undesirable reflex mechanisms. Use of the stepped-care approach does not take into account fundamental hemodynamic differences associated with a hypertensive patient's age, race and weight. A nonphysiologic approach in the use of antihypertensive agents may be associated with progression of left ventricular hypertrophy, metabolic derangements, arrhythmias, sudden death, and increased atherosclerotic and nephrosclerotic complications. Considerations of the alterations in cardiovascular structure that can occur in light of the activity of the renin-angiotensin system, the sympathetic nervous system and transcellular calcium flux are discussed as to how they affect long-term survival.

Aging↗
PubMed1988

The relationship between sexual maturity rating, age, and increased blood pressure in adolescents.

Blood pressure values are known to vary with age and body size. The effect of sexual maturity was explored in 746 patients in an adolescent clinic. Systolic blood pressure for boys and girls showed an increase with a change from Tanner stage 2 to 3. Diastolic blood pressure did not increase. Both systolic and diastolic blood pressures showed a weight effect that was generally maintained within the Tanner stages. The gradual increase in blood pressure for large groups of adolescents would appear to be the result of the aggregate increase in size (weight) resulting from the asynchronous growth spurts of individuals studied. Consequently, those individuals with a strikingly early or late onset of maturation may have erroneous interpretations of their blood pressure. As biologic outliers, the borderline hypertensive who matures early may be overidentified, while the late maturer might go unrecognized.

Adolescent↗
PubMed1988

Atypical idiopathic hypercalciuria in an adolescent.

Idiopathic hypercalciuria (IH) in adults is recognized as a cause of urolithiasis. If IH is symptomatic, the symptoms are hematuria, renal colic, or obstructive uropathy with or without infection. In children, IH has been linked to the spectrum of urinary symptoms including hematuria, pyuria, dysuria, recurrent urinary infections, abdominal or suprapubic pain, proteinuria, and the frequency-urgency syndrome. Hematuria may appear prior to the appearance of stones, and thiazide therapy appears to prevent stone formation by decreasing urinary calcium excretion. This report describes an older adolescent with hematuria and flank pain. His urinary chemistry values were not consistently typical of IH, but a thiazide trial with withdrawal challenge was diagnostic. His case is remarkable because, though essentially an adult, his disease was typical of prepubertal disease. Adolescents with unexplained urinary symptoms should be evaluated for IH. The urinary calcium-creatinine ratio may not be elevated, and timed urinary calcium may be equivocal. In some cases a thiazide trial may be valuable and cost effective.

Adolescent↗
PubMed1988

Incidence and morbidity of cytomegalovirus disease associated with a seronegative recipient receiving seropositive donor-specific transfusion and living-related donor transplantation. A multicenter evaluation.

This retrospective study was conducted to identify the frequency of cytomegalovirus (CMV) disease in seronegative recipients of donor-specific transfusion (DST) and living-related donor (LRD) kidneys from seropositive donors. A total of 151 LRD transplants (TX) were performed at six transplant centers over a 3-year period. A total of 33 patients were identified as having been seronegative (pre-TX) for CMV, yet they had DST and a TX from a seropositive LRD. Of these patients, 12 (36.4%) seroconverted within the first 6 months post-TX and developed clinical CMV disease. Additional patients seroconverted, but did not have evidence of clinical disease and were not tested further. All TX centers, with the exception of one, had seronegative patients that became ill after receiving a seropositive DST/LRD TX. Six patients manifested their disease as a febrile illness with leukopenia and liver enzyme elevations, four had pneumonitis, and two developed CMV ulcerations of the colon (one of whom died from resultant sepsis). Of the 36 seronegative patients who received seronegative DST/LRD TX none became ill with CMV disease. Of the 72 seropositive patients who received DST/LRD TX, only 2 (2.8%) developed CMV illness (one, seropositive into seropositive, the other, seronegative into seropositive). Of the 33 seronegative patients receiving seropositive DST/LRD TX, 17 received antilymphocyte preparations (ALP), and 8 of these became ill (47.1%). Of 16 patients not receiving ALP, 5 (31.3%) developed clinical CMV illness. Of the 33 patients who were identified as having been seronegative for CMV yet received seropositive DST/LRD TX, the 12 who did develop CMV illness had two graft losses, one death, and a serum creatinine for the remaining 9 patients of 2.3 +/- 1.6 at last follow-up. The remaining 21 patients who developed no illness had a serum creatinine of 1.3 +/- 0.6 with no graft losses at the last follow-up. This evidence suggests that a prospective TX recipient who is seronegative for CMV who receives DST/LRD TX from a seropositive family member has a significant risk for developing morbidity related to clinical CMV illness.

Adolescent↗