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Biomedical subjects

A Forster

Publications and source records attributed to A Forster.

At least 181 records · Page 10Linked to original sources

Absence of benefit of incentive spirometry in low-risk patients undergoing elective cholecystectomy. A controlled randomized study.

To determine the potential benefit of incentive spirometry, which has been advocated to prevent pulmonary complications after upper-abdominal surgery, we compared a group of patients receiving incentive spirometry to another group receiving no specialized postoperative respiratory care. Forty patients in the American Society of Anesthesiologists' class 1 and 2 who were undergoing cholecystectomy (through right subcostal incision) were included in the study and were randomly allocated to one of the two groups. Patients receiving incentive spirometry were encouraged by a specialized respiratory physiotherapist to breathe deeply for five minutes hourly, 12 times daily, for three postoperative days. No statistically significant difference between the two groups was found in the radiologic evidence of postoperative pulmonary complications, arterial oxygen pressure, spirometric measurement, and clinical evaluation at the second or fourth postoperative day (or both). In particular, deterioration on the chest x-ray film at the fourth postoperative day was observed in eight of 20 patients in the group receiving incentive spirometry and in six of 20 in the control group. Our study confirms the postoperative deterioration of respiratory function after upper-abdominal surgery and demonstrates the lack of therapeutic values of incentive spirometry in these patients at low risk for pulmonary complications.

Adult↗

Calcium-channel inhibition in pheochromocytoma.

Nifedipine, a calcium-antagonist and potent vasodilator, was tested in three patients with pheochromocytoma. In two patients who were normotensive, nifedipine prevented a rise in blood pressure but not in plasma epinephrine and norepinephrine following the iv injection of the dopamine-antagonist metoclopramide. In another patient who was hypertensive, nifedipine was as effective in lowering blood pressure as labetalol or phenoxybenzamine, and did not modify the elevated plasma and urinary catecholamines. Nifedipine appears to control hypertension in pheochromocytoma, without altering catecholamine levels, suggesting that calcium-channel blockade interferes with catecholamine vascular action but not with tumoural catecholamine release. Calcium-antagonists may be helpful in preventing the pressor complications of provocative tests used in the screening of pheochromocytoma.

Adrenal Gland Neoplasms↗

Organization of the T-cell receptor alpha-chain gene and rearrangement in human T-cell leukaemias.

The structure and rearrangement of the human T-cell receptor alpha-chain gene have been analysed. The constant region segment is comprised of four exons, with the 3' non-coding region present as a separate exon. Two J alpha segments have been identified by sequence analysis about 4 X 10(3) and 15 X 10(3) base-pairs upstream from the constant region segment. Analysis of alpha-chain rearrangements in a panel of T-cells reveals the presence of at least four more J alpha segments within 19 X 10(3) base-pairs of C alpha and suggests the existence of additional J alpha segments further upstream. This dispersed organization of the J alpha region contrasts with the clustered organization observed in other lymphoid rearranging genes. The use of J alpha probes in diagnostic purposes for T-cell leukaemia is not, therefore, convenient and will require a number of different probes to ensure complete analysis of the locus.

Base Sequence↗

Truncation of exon 1 from the c-myc gene results in prolonged c-myc mRNa stability.

The human c-myc gene consists of three exons transcribed from two distinct promoters and the function of the first, noncoding exon is unknown. In COLO 320 cells, there co-exist normal and truncated (i.e., lacking exon 1) c-myc genes, both of which are transcribed. Studies on the turnover of c-myc mRNA show that the normal mRNA has an in vivo half-life of approximately 30 min which is approximately similar to the turnover time of the mRNA in lymphoblastoid cells. However, the truncated mRNA was found to be substantially more stable. This observation was also made with a Burkitt's lymphoma cell line which has a translocated, truncated c-myc gene. Therefore truncation of the c-myc gene can cause the mRNA to be more stable than the full size product suggesting that this can be a crucial factor in the activation of the c-myc oncogene, by exon 1 loss, in chromosomal translocation. The results also suggest a role for exon 1 in the c-myc mRNA degradative mechanism.

Base Sequence↗

Metabolism of c-myc gene products: c-myc mRNA and protein expression in the cell cycle.

The presence and synthesis of c-myc protein and mRNA in the cell cycle has been studied. We find that c-myc mRNA is present, at equivalent levels, at all times in the cell cycle with the possible exception of mitosis. Furthermore, we demonstrate that this mRNA is transcribed in both G1 and G2 phases. An analysis of the c-myc protein in vivo shows that de novo synthesis occurs in G1 and G2 and the protein turns over with a half-life of approximately 20-30 min in both phases. Furthermore, the level of c-myc protein rapidly increases in cell populations when they re-initiate the cell cycle, thereafter decreasing as the culture reaches quiescence. The results therefore suggest that expression of c-myc can be rapidly modulated and that it is activated during the G0 to G1 transition, but is expressed thereafter in the cell cycle.

Animals↗

Heterogeneity of T-cell beta-chain gene rearrangements in human leukaemias and lymphomas.

The state of T-cell receptor beta-chain gene rearrangement in human T-cell leukaemias has been analysed. All forms of leukaemia tested (T-CLL, ALL, PLL, Sezary syndrome and ATL) exhibit rearrangements of C beta genes confirming the clonality of these neoplasias. However we find no evidence for common gene rearrangements nor for restricted rearrangement patterns within this type of neoplasia. We find evidence of T-cells with C beta 1 and C beta 2 rearrangements, sometimes associated with Igh JH rearrangements, but several cases of T-cell leukaemia with a marker inversion of chromosome 14 (q11;q32) do not have Igh JH rearrangements. The results suggest that TCR beta gene rearrangement occurs early in T-cell ontogeny but that this rearrangement is most often irrelevant to leukaemogenesis.

Cell Line↗

Chromatin structure of transcriptionally active and inactive human c-myc alleles.

To help elucidate the mechanism of regulation of the c-myc gene we have characterised the DNase I hypersensitive sites around this gene in the human promyelocytic leukaemia cell line HL60, which carries amplified c-myc, and in Ramos, a Burkitt's lymphoma cell line with a translocation close to exon 1 of c-myc. Although dividing HL60 cells display a pattern of DNase I hypersensitive sites which is similar to that of previously described c-myc genes in B cells (lymphoblastoid and Burkitt's lymphoma), changes were found in DNase I hypersensitive sites upon differentiation of the HL60 cell line (accompanied by decreased c-myc transcription). Lack of c-myc transcription coincides with the loss of several DNase I hypersensitive sites and the reduction in intensity of a further site. A similar pattern was also seen in the inactive allele of the Burkitt's lymphoma cell line Ramos. A striking feature of both differentiated HL60 cells and of the inactive allele in Ramos is the quantitative maintenance of a DNase I hypersensitive site which occurs approximately 2.5 kb upstream of the c-myc gene promoters.

Alleles↗

Sequence and evolution of the human T-cell antigen receptor beta-chain genes.

We present the nucleotide sequences of the two genomic constant (C)-region gene segments, C beta 1 and C beta 2, encoding the beta chain of the human T-cell antigen receptor. The two C beta genes are organized identically to each other and to the corresponding mouse genes, both having four exons, whose boundaries were confirmed from the sequence of a C beta 2 cDNA clone from the T-cell line MOLT-4. The predicted amino acid sequences of human C beta 1 and C beta 2 differ at only five positions, which suggests that the proteins have very similar functions. This similarity is the result of strong nucleotide-sequence conservation in protein-coding regions, which extends to silent positions. A quantitative analysis of an alignment of the nucleotide sequences of the two human genes shows that whereas the 5' ends (including the first exon) are extremely homologous, the 3' ends are widely divergent, with other regions having intermediate levels of homology. Analysis of published data [Gascoigne, N.R.J., Chien, Y., Becker, D.M., Kavaler, J. & Davis, M.M. (1984) Nature (London) 310, 387-391] shows that the mouse C beta 1 and C beta 2 genes are also virtually identical in their first exons but more divergent in the remaining coding regions. Therefore, partial gene conversion events may have occurred during the evolution of both human and mouse C beta genes.

Amino Acid Sequence↗

Evaluation of I.V. labetalol for treatment of posttraumatic hyperdynamic state.

A hyperdynamic state, characterized by an elevated blood pressure and tachycardia is frequently seen during the first few days following severe multiple trauma. We examined the cardiovascular effects of the alpha and beta adrenoceptor blocking agent labetalol in patients presenting a hyperdynamic cardiovascular state some days after major trauma. Ten patients with a heart rate-systolic blood pressure product (RPP) of more than 2000 during 6 consecutive hours, despite normovolaemia, adequate ventilation, analgesia and sedation were investigated. After a mean dose of 2.1 +/- 1.2 mg X kg-1 (mean +/- SD) of labetalol injected intravenously over a 10-min period, heart rate decreased from 117 +/- 28 to 102 +/- 19 beats X min-1, systolic arterial pressure from 25 +/- 3.5 to 18.5 +/- 2.7 kPa, diastolic pressure from 11 +/- 1.7 to 9.5 +/- 1.7 kPa, mean arterial blood pressure from 15.5 +/- 2.1 to 12.4 +/- 2.1 kPa, and the RPP from 2880 +/- 867 to 1853 +/- 373. The beneficial effect of this dose lasted 24 h in 8 of 10 patients without additional administration. No important side effects such as cardiac arrhythmias, hypotension, or bronchospasm were noted. We conclude that labetalol used in fractional intravenous doses permits an adequate treatment of a "hypertension-tachycardia syndrome" in severely injured patients.

Adult↗

[Prevention of hyperkalemia and muscular fasciculations induced by suxamethonium].

Suxamethonium has not yet been replaced to ease endotracheal intubation despite its many undesirable side effects. Hyperkalemia and muscle pain are two such side effects; they are not reliably prevented by giving, before suxamethonium, a small dose of a non depolarizing muscle relaxant, although it does decrease muscle fasciculations. The purpose of this study was to compare with a control group three different pretreatments of these undesirable effects of suxamethonium: 1) hyperventilation, 2) calcium chloride which are accepted means of lowering the serum potassium, and 3) magnesium sulfate which has been reported in a non-controlled study to decrease muscle fasciculations. The study was performed in 40 patients (10 per group) in whom changes of plasma potassium and calcium levels were determined and muscle fasciculations measured by an objective method. Serum electrolyte variations and the quantity and duration of muscle fasciculations were similar in all groups. None of the pretreatments administered had any adverse effect on the neuromuscular block induced by suxamethonium.

Adolescent↗

Effects of infrarenal aortic cross-clamping on renal hemodynamics in humans.

While the systemic cardiovascular consequences of infrarenal aortic cross-clamping during aortic abdominal surgery are well documented, its repercussions on renal hemodynamics in humans have not been reported. In 12 patients, scheduled for elective aortic surgery, renal clearances, using 51Cr EDTA and 125I hippuran, were measured before, during, and after infrarenal aortic cross-clamping. A continuous infusion of mannitol 20% at a rate of 100 ml/h was administered throughout the study. Arterial and renal venous blood sampling, obtained at the midpoint of each period, permitted calculation of the extraction fraction of 125I hippuran and accurate determination of renal blood flow and its cortical-extracortical distribution. Although cardiac output and systemic vascular resistance did not change significantly between the three study periods, infrarenal aortic cross-clamping decreased 125I hippuran clearance by 29 +/- 15% (P less than 0.05) and renal blood flow by 38 +/- 14% (P less than 0.001). Simultaneously, an increase of 75 +/- 31% in renal vascular resistance (P less than 0.05) was observed and the extraction fraction of 125I hippuran increased from 0.67 +/- 0.05 to 0.74 +/- 0.05 (P less than 0.01). All of these changes, which indicate global diminution of renal perfusion with a redistribution of renal blood flow toward the cortical compartment, persisted for at least 1 h after release of the aortic clamp. Early signs of renal tubular damage, such as the appearance of lysozyme and ligandine in the urine, however, were never observed. The authors conclude that infrarenal aortic cross-clamping produces profound and sustained alterations in renal hemodynamics and may be harmful in patients with impaired renal function or when surgical occlusion of the aorta is prolonged.

Aged↗

Effect of intravenous midazolam on breathing pattern and chest wall mechanics in human.

Breathing pattern, thoracoabdominal motion, and separate end-expiratory positions of the rib cage and abdomen were measured noninvasively in eight healthy subjects before and after intravenous administration of either placebo or midazolam, a short-acting benzodiazepine. Compared with placebo, midazolam produced a significant (P less than 0.01) decrease in mean inspiratory flow of 29% from preinjection values, resulting in a 39% reduction in tidal volume (VT). This ventilatory depression was partly compensated by a 35% decrease in expiratory time producing an increase in respiratory rate (+39%). The fall in VT was almost entirely (91%) mediated by a reduction of the abdominal contribution to tidal breathing while sparing rib cage motion. This fact contrasts with the effects of inhalational anesthetics or morphine, which preferentially depress rib cage expansion, indicating that thoracoabdominal motion may selectively be depressed by different pharmacological agents. In addition, continuous recording of end-expiratory levels showed a significant transient fall in the rib cage's end-tidal position 2 min after midazolam administration associated with the occurrence of central apneas.

Abdominal Muscles↗

c-myc Gene activation and chromosomal translocation.

Burkitt's lymphoma cells are characterized by the presence of specific chromosomal translocation bringing the immunoglobulin and the c-myc proto-oncogenes into the proximity of each other. Different translocations involve each of the three immunoglobulin loci but the breakpoint with respect to the c-myc gene is shown to be very variable. In t8/14 the breakpoint occurs upstream from the c-myc gene whilst in the variant lymphomas it occurs downstream from the gene. Possible ways in which the translocation affects the c-myc gene are discussed.

Animals↗