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Biomedical subjects

B Kramer

Publications and source records attributed to B Kramer.

At least 145 records · Page 8Linked to original sources

Cancer chemotherapy associated symptomatic stomatitis: role of Herpes simplex virus (HSV).

The relationship between oral shedding of Herpes simplex virus (HSV) and cytotoxic cancer chemotherapy was studied. HSV seropositive outpatients receiving cytotoxic chemotherapy had HSV recovered from throat washings in eight of 114 patients (7.0%), significantly more often than HSV seropositive outpatients with malignancy who were not receiving cytotoxic chemotherapy (one of 91 patients; 1.1%; P = 0.04). Twenty-eight HSV seropositive chemotherapy patients and 11 HSV seropositive healthy hospital personnel were studied serially 2-3 times per week over a 3-4 week period for oral HSV shedding. Although a comparable percentage of each group shed HSV at least once (57.1% of chemotherapy patients versus 36.4% of controls), chemotherapy patients had a strikingly higher incidence of multiple positive cultures: 40/218 attempts (18.7%) versus 4/156 attempts (2.6%) for controls (P less than 10(-5)). Among chemotherapy patients who developed clinically evident stomatitis, 12 of 14 (85.7%) had HSV recovered compared to four of 14 (28.6%) without lesions (P = 0.004). We conclude that while oral mucosal HSV infection is associated with symptomatic stomatitis following chemotherapy, HSV does not account for all mucosal lesions in chemotherapy patients.

Antibodies, Viral↗

Acute and long-term effects of captopril on exercise cardiac performance and exercise capacity in congestive heart failure.

Although many studies have shown that captopril (CPT) provides acute hemodynamic improvement in patients with severe congestive heart failure (CHF) at rest, little information is available concerning exercise hemodynamic responses to CPT or the effect of this drug on exercise tolerance in CHF. Therefore, we evaluated the hemodynamic effects of CPT at rest and during upright bicycle exercise in 15 patients with stable CHF. CPT (25 to 50 mg) reduces both resting heart rate and mean arterial pressure (84 +/- 11 to 78 +/- 7 bpm, p less than 0.025 and 85 +/- 9 to 64 +/- mm Hg, p less than 0.001). Concomitantly, left ventricular filling pressure dropped dramatically (26 +/- 9 to 15 +/- 7 mm Hg, p less than 0.001), while cardiac and stroke indices rose (2.0 +/- 0.5 to 2.5 +/- 0.6 L/min/m2, p less than 0.001, and 25 +/- 8 to 33 +/- 7 ml/m2, p less than 0.001). Similar directional changes occurred during exercise, with heart rate, mean arterial pressure, and left ventricular filling pressure at maximum exercise being less (123 +/- 15 to 115 +/- 16 bpm, p less than 0.01; 93 +/- 17 to 86 +/- 14 mm Hg, p less than 0.05; and 35 +/- 10 to 30 11 mm Hg, p less than 0.001, respectively) after CPT ingestion. Peak exercise cardiac index rose slightly (3.6 +/- 0.7 to 3.9 +/- 0.6 L/min/m2) but not significantly. Six patients followed long term on CPT underwent elective recatheterization after 3 months. In these, the beneficial hemodynamic changes seen acutely persisted or further improvement was noted, both at rest and during exercise. Most impressively, peak exercise cardiac index rose from 3.6 +/- 0.7 to 4.6 +/- 1.0 L/min/m2 (p less than 0.05), and this was associated with an increase in exercise duration (8.0 +/- 2.2 to 11.5 +/- 1.4 minutes, p less than 0.05) and exercise work load (332 +/- 32 to 468 +/- 52 kp-m/min, p less than 0.05). These findings indicate that in patients with severe CHF, oral CPT provides markedly beneficial augmentation of cardiac function during activity as well as at rest; moreover, chronic CPT therapy substantially increases exercise capacity in this setting.

Aged↗

Hemodynamic differences between supine and upright exercise in patients with congestive heart failure.

Although the differences in hemodynamic responses to supine and upright exercise have been studied in normal subjects and in patients with angina pectoris, no such comparison has been made in patients with congestive heart failure. Many investigators measure exercise hemodynamics in heart failure patients to assess the effect of vasodilator and inotropic drugs. Both modes of exercise have been used and have often yielded differing results. We compared the hemodynamic response to supine and upright exercise in 14 patients with stable, New York Heart Association class III chronic heart failure. During upright exercise, peak heart rate was higher (124 +/- 15 vs 115 +/- 18 beats/min, p less than 0.025) and peak mean arterial pressure was lower (102 +/- 15 vs 95 +/- 17 mm Hg, p less than 0.25), yielding similar double products. Although the peak left ventricular filling pressure was slightly lower during upright exercise (40 +/- 7 vs 35 +/- 10 mm Hg, p less than 0.05), the maximum cardiac and stroke indexes were not significantly different (3.6 +/- 0.8 vs 3.4 +/- 0.8 l/min/m2 and 30 +/- 8 vs 30 +/- 6 ml/m2, upright vs supine exercise). In contrast to these relatively similar hemodynamic responses, exercise capacity was significantly greater during upright exercise (peak work load 336 +/- 84 vs 293 +/- 73 kpm/min, p less than 0.1; maximum oxygen consumption 12.1 +/- 2.4 vs 9.8 +/- 1.9 ml/min/kg, p less than 0.001). We conclude that either exercise method may be used to assess the hemodynamic effects of drugs, but that exercise capacity should be measured in the upright position.

Aged↗

Comparison of myocardial thallium-201 clearance after maximal and submaximal exercise: implications for diagnosis of coronary disease: concise communication.

Recently the quantitation of regional thallium-201 clearance has been shown to increase the sensitivity of the scintigraphic detection of coronary disease. Although TI-201 clearance rates might be expected to vary with the degree of exercise, this relationship has not been explored. We therefore evaluated the rate of decrease in myocardial TI-201 activity following maximal and submaximal stress in seven normal subjects and 21 patients with chest pain, using the seven-pinhole tomographic reconstruction technique. In normals, the mean TI-201 clearance rate declined from 41% +/- 7 over a 3-hr period with maximal exercise to 25% +/- 5 after 3 hr at a submaximal level (p less than 0.001). Similar differences in clearance rates were found in the normally perfused regions of the left ventricle in patients with chest pain, depending on whether or not a maximal end point (defined as either the appearance of ischemia or reaching 85% of age-predicted heart rate) was achieved. In five patients who did not reach these end points, 3-hr clearance rates in uninvolved regions averaged 25% +/- 2, in contrast to a mean of 38% +/- 5 for such regions in 15 patients who exercised to ischemia or an adequate heart rate. These findings indicate that clearance criteria derived from normals can be applied to patients who are stressed maximally, even if the duration of exercise is limited, but that caution must be used in interpreting clearance rates in those who do not exercise to an accepted end point.

Adult↗

Vasodilator treatment with isosorbide dinitrate and hydralazine in chronic heart failure.

Several reports have suggested that because isosorbide dinitrate and hydralazine have different and additive haemodynamic effects at rest in patients with chronic heart failure, these agents should be administered in combination. Some studies, however, indicate thay they are effective individually as well. Since most patients with heart failure are symptomatic only with activity, we examined the haemodynamic effects of these drugs given individually and in combination, at rest and during upright bicycle exercise. As has been noted previously, at rest isosorbide significantly lowered both ventricular filling pressures and did not change cardiac output; hydralazine increased cardiac output and had only a slight effect on pulmonary capillary wedge pressure; combined treatment produced both beneficial effects. In contrast, during exercise isosorbide dinitrate also raised cardiac output while hydralazine more dramatically lowered the wedge pressure. Combined treatment produced significantly greater improvement in each haemodynamic index than either drug alone, with a resulting 54 per cent increase in exercise cardiac output, and a 33 per cent reduction in exercise wedge pressure. Maximal oxygen consumption increased acutely during combined treatment. These findings suggest that isosorbide dinitrate and hydralazine may each be effective in some patients, but that they are even more beneficial in combination.

Adult↗

Postural hypotension and tachycardia during hydralazine--isosorbide dinitrate therapy for chronic heart failure.

Supine and upright hemodynamic measurements were performed in 10 patients with chronic congestive heart failure, before and during vasodilator therapy with hydralazine and isosorbide dinitrate. This combination of drugs produced significant improvement in supine hemodynamic measurements, with the pulmonary capillary wedge pressure decreasing from 26 +/- 5 to 18 +/- 5 mm Hg (mean +/- SD, p less than 0.01) and stroke volume index increasing from 25 +/- 6 to 39 +/- 6 ml/m2 (p less than 0.01), without any significant change in heart rate (HR) or mean arterial pressure (MAP). However, with the patients upright, HR rose significantly (87 +/- 17 to 99 +/- 17 beats/min, p less than 0.05) and MAP fell (84 +/- 10 to 66 +/- 11 mm Hg, p less than 0.001) compared with measurements before treatment. These patients also exhibited potentially deleterious postural changes in HR, MAP, cardiac output, stroke volume index and stroke work index during therapy with the combination of hydralazine and isosorbide dinitrate. Although diuretic therapy (which had been withheld for 12 hours in eight subjects but only for 6 hours in two others) may have played a role in producing these changes, postural hypotension or tachycardia was not noted before vasodilator therapy or during therapy with nitrates or hydralazine. Repeat catheterization after 3 months in six patients revealed a lessening of the postural effects. These findings indicate the need to perform upright as well as supine hemodynamic measurements during the initiation of vasodilator therapy and suggest the need for particular caution in patients with ischemic heart disease.

Heart Failure↗

Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance.

The acute hemodynamic response to vasodilators in patients with chronic heart failure has been well characterized, but less is known about the long-term hemodynamic effects of vasodilator therapy. We measured hemodynamic variables at rest and during upright exercise in 11 patients during the initiation of therapy with oral hydralazine and sublingual isosorbide dinitrate and, in eight of these, after 3 months of continuous treatment. Marked initial increases in resting cardiac output and stroke volume and reductions in wedge pressure were sustained during chronic therapy. Similarly, the early improvement in exercise hemodynamic measurements persisted in most subjects. Exercise tolerance, quantified as the maximum duration of treadmill exercise, increased modestly (7.7 +/- 2.6 to 8.9 +/- 3.3 minutes, 0.05 less than p less than 0.10) after several days on vasodilators and further (10.2 +/- 3.7 minutes, p less than 0.01) during long-term treatment. The acute hemodynamic effects of vasodilator therapy at rest or during exercise did not correlate well with the changes in exercise tolerance. Our findings suggest that the combination of hydralazine and isosorbide dinitrate improves cardiac performance at rest and during exercise in patients with chronic heart failure and that this improvement persists during chronic therapy. In most patients, this hemodynamic improvement is accompanied by greater exercise tolerance.

Acute Disease↗

Arched gonadal arteries in the South African negro.

The frequency with which the gonadal arteries follow a recurrent course, upwards and arching over the renal veins before descending to the gonads, is recorded for the South African Negro. The gonadal arteries follow such a course on the left side in 17, 2% and on the right side in 22% of cases. This incidence for arched left sided arteries is comparable to that recorded in other studies, but the frequency for arched right sided arteries in the South African Negro appears to be higher. Recognition of arching gonadal arteries is of importance to the vascular surgeon and urologist.

Arteries↗

Is there a ventral neural ridge in chick embryos? Implications for the origin of adenohypophyseal and other APUD cells.

Two- to ten-somite chick embryos were studied in order to ascertain whether, as has been proposed, there exists a 'ventral neural ridge' which gives rise to the hypophyseal (Rathke's) pouch. Serial sections and stereo-microscopy were used. The neural ridges arch around the rostral end of the embryo onto the ventral surface of the head, but no evidence was found for their extension to form a 'ventral neural ridge' reaching the stomodaeum: in fact a considerable expanse of non-thickened surface ectoderm was seen to separate the ventral portions of the neural ridges from the stomodaeum. The thickening of neural ectoderm which does appear on the ventral surface of the head results from apposition and fusion of the opposite neural ridges flanking the neural plate and thus the tip of the anterior neuropore--the classically accepted mode of closure of the neuropore. These findings are in accord with the generally accepted concept of the origin of the hypophyseal pouch rather than with its derivation from a 'ventral neural ridge'. No sign of neural crest formation was encountered ventrally; this observation excludes the possibility that endocrine cells of the APUD series could originate from neural crest in this region.

APUD Cells↗

The effect of actinomycin D on the nucleolus and on pigment synthesis in pigment cells of Xenopus laevis: an ultrastructural study.

The effect of AMD on the nucleolus and on melanogenesis in differentiating pigment cells of Xenopus laevis was investigated in cultured neural crest cells. Cultures were treated with either 2 or 10 microgram/ml AMD for 41/2 hours. Following treatment the antibiotic was removed. Observations of the cells were made with both scanning and transmission electron microscopes. Actinomycin D almost entirely stopped pigment formation in neural crest cultures during treatment. The morphological sequence in the formation of melanin granules in the untreated pigment cells appears to be as follows: The earliest identifiable premelanosome is membrane-bound and contains very thin laminae and/or small vesciles. The premelanosomes become until they are approximately the size of mature melanin granules and there is thickening of the laminae, which appear to have a periodic substructure. The cells eventually become packed with electron-dense melanin granules. Compared with controls, the cytoplasm of treated cells showed a greater abundance of smooth- than of fuzzy-membraned vesicles, less rough endoplasmic reticulum, dilatation of the Golgi cisternae, and a smaller number of premelanosomes. The necleolus showed segregation and blebbing of its components, decrease in size and even disappearance; sometimes confluence of the components occurred. The most consistent morphological effect of AMD on the nucleolus was the separation of the fibrillar and granular areas. The granular component appeared to undergo marked changes in size and arrangement and is thought to be the source of ribosomal RNA precursors. The alteration in size of the outer component of the nucleolus went hand in hand with disappearance of free ribosomes from the cytoplasm of treated cells and inhibition of pigment synthesis.

Animals↗

An experimental investigation into the possible origin of pancreatic islet cells from rhombencephalic neurectoderm.

To determine whether or not any pancreatic islet cell type arises from rhombencephalic levels of neurectoderm, lengths of presumptive rhombencephalon (containing potential neural crest) of Black Australorp chick embryos at 6- to 9-somite stages were replaced isotopically and isochronically by neural tube of Japanese quail embryos. Some transplants included mesencephalic regions. In some cases various levels of the rhombencephalon were deleted and not replaced. The quail nuclear marker was detected in cranial ganglia in operated embryos sacrificed at 3 3/4 days of incubation and in enteric ganglia and cells accompanying some pancreatic nerves, in embryos killed at 7 days of incubation. This provided evidence of normal migration of crest cells from the grafts. Dopa was administered to the younger embryos, which were submitted to the formaldehyde-induced fluorescence procedure to demonstrate APUD (Amine Precursor Uptake and Decarboxylation) cells. No pancreatic APUD cells exhibited the quail nuclear marker. In 9- to 11-day embryos, A and B cells were identified by specific light and electron microscopic features. None showed the quail marker. The marker was also absent from those D cells seen and from cells of an as yet unidentified type, but not enough of these were found to warrant a conclusion. All islet cell types were found in embryos from which various levels of the rhombencephalon had been deleted. It is concluded that at least A and B islet cells are not derived from the rhombencephalic neurectoderm and probably not from mesencephalic levels. Their most likely origin remains the endoderm, which was the accepted source until recently.

APUD Cells↗