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Biomedical subjects

L Jackson

Publications and source records attributed to L Jackson.

At least 109 records · Page 6Linked to original sources

Trisomy 16 confined to chorionic villi and unfavourable outcome of pregnancy.

Two cases of trisomy 16 confined to placental tissue associated with an unfavourable outcome of the pregnancy are reported. In the first case, after a diagnosis of an apparent non-mosaic trisomy 16 at chorionic villi sample (CVS), an intrauterine fetal death occurred at the 22nd week. In the second case a mosaic with trisomy 16 was found in chorionic villi and the fetus was still-born at 38 weeks. From a comparison of their cases with those of the literature, the authors conclude that a trisomy 16 confined to placental tissue has a negative effect on fetal growth and pregnancy outcome.

Adult↗

Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening.

BACKGROUND: In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS: To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. CONCLUSIONS: These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.

Action Potentials↗

A prospective study of patient choice in treatment for primary breast cancer.

One hundred and sixty-three patients with primary breast cancer were prospectively studied. Using recently developed selection criteria 91 patients were offered a choice of treatment. Forty-one chose to undergo conservation treatment and 47 chose to undergo simple mastectomy. In those women who were offered a choice of treatment there was a significant tendency for younger patients to choose breast conserving treatment.

Adult↗

Kinetics of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641) in humans.

The metabolism and disposition of LY186641, a diarylsulfonylurea with antineoplastic activity identified in preclinical tests, was determined in 21 patients who received 23 courses of orally administered drug. A linear correlation was found between the dose of drug administered and LY186641 peak plasma concentrations and LY186641 area under the curve measurements. Clearance (135 +/- 36 ml/h/m2), terminal half-life (31 +/- 11 h), and volume of distribution (10.2 +/- 2.8 liters) were independent of drug dose. No LY186641 was excreted in urine. Hydroxy and keto metabolites of LY186641 were identified in plasma and urine samples. Urinary excretion of these metabolites during the initial 48 h following drug administration accounted for 20% of LY186641 disposition. Plasma half-life of the hydroxy and keto metabolites was longer than that of parent drug (3.3 and 3.1 days, respectively). Plasma concentrations of parent drug correlated with the presence of methemoglobinemia, the dose-limiting toxicity found with LY186641.

Administration, Oral↗

Cornelia de Lange syndrome. Otolaryngologic manifestations.

Cornelia de Lange syndrome (CDLS) is characterized by multiple congenital malformations and mental retardation. New studies have documented otolaryngologic abnormalities. We examined 45 patients with CDLS. Virtually all had hearing loss, and most had impaired language development. Other otolaryngologic abnormalities, including external auditory canal stenosis and cleft palate, were also common. Because of the high incidence of otolaryngologic abnormalities, and the need for early intervention, it is important for otolaryngologists to recognize CDLS manifestations in the head and neck.

Adolescent↗

De novo direct tandem duplication of the short arm of chromosome 7(p21.1-p14.2).

We report on a 6-year-old boy with moderate developmental retardation and unusual dermatoglyphics. Cytogenetic analysis demonstrated a duplication of chromosome sub-region 7p21.2-p14.2. Confirmation of the specific duplicated region was determined by quantitative Southern blotting by using a DNA fragment previously localized to the portion of chromosome 7 thought to be duplicated. This patient did not have the internal malformations seen with other dup(7p) patients.

Blotting, Southern↗

Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study.

Cytogenetic results of first-trimester chorionic villus sampling are reported from seven U.S. medical centers. For 6033 patients who had a successful chorionic villus sampling procedure, the rate for obtaining a cytogenetic diagnosis was 99.6% with the direct method, long-term culture, or both. There were no incorrect sex predictions and no diagnostic errors involving trisomies 21, 18, or 13, sex chromosome aneuploidies, or structural abnormalities. There were no cases of normal cytogenetic diagnosis followed by birth of a cytogenetically abnormal infant. Three cases of unusual aneuploidies (tetraploidy, trisomy 16, and trisomy 22) detected by the direct method only were not confirmed by cytogenetic follow-up. Mosaic cytogenetic abnormalities were observed in 0.83% of all cases in which chorionic villus sampling was done but were confirmed by amniocentesis or in fetal tissues in only 7 of 30 cases (23.3%). Maternal cell contamination occurred in 1.9% of long-term cultures, although this did not present any cytogenetic diagnostic difficulties. Overall, a very high degree of laboratory success and diagnostic accuracy was observed with either cytogenetic method, although fewer predictive errors were observed with the long-term culture method and none were observed when both methods were used.

Amniocentesis↗

Goserelin (Zoladex) in premenopausal advanced breast cancer: duration of response and survival.

In premenopausal women with advanced breast cancer the luteinising hormone-releasing hormone agonist goserelin (Zoladex, ICI plc) will produce serum levels of oestradiol equivalent to those following surgical oophorectomy or the menopause. This paper reports our further experience of using this drug in 75 premenopausal patients with advanced breast cancer. In addition to response rates, duration of response is reported. An objective response was seen in 25 patients (33%), the median duration of which was in excess of 15 months. Seven patients (9%) showed a complete response to therapy; median duration greater than 37 months. There was no significant difference in time to disease progression (Lee-Desu statistic 18.26, 1 d.f., P = 0.43) and probability of survival (Lee-Desu statistic 3.41, 1 d.f., P = 0.07) between those patients assessed as having either static disease, or those showing a partial response at six months. Response to therapy correlates significantly with the oestrogen receptor status of the primary tumour (X2 = 20.59, 6 d.f., P less than 0.005). The modest side-effects, ease of administration and reversibility make this approach to therapy very attractive. This is to be remembered in that 53% of patients had disease progression whilst receiving goserelin. These patients thus avoided the unnecessary and irreversible morbidity associated with surgical oophorectomy. With the proven efficacy and minimal morbidity associated with goserelin we believe there is no current role for surgical oophorectomy in the management of premenopausal patients with advanced breast cancer.

Adult↗

Terfenadine, a potent histamine H1-receptor antagonist in the treatment of grass pollen sensitive asthma.

1. We have assessed the effect of a specific histamine H1-receptor antagonist, terfenadine, in the treatment of atopic asthmatics during the grass pollen season. 2. Eighteen mild, grass pollen sensitive asthmatics (10F, 8M, mean +/- s.e. mean age 34.7 +/- 5.6 years), all of whom were controlled on inhaled beta 2-adrenoceptor agonists alone, took part in a 9 week, double-blind, crossover study using terfenadine 180 mg three times daily and placebo. Throughout the study patients recorded peak expiratory flow rate (PEFR) twice daily, symptoms of cough, wheeze, breathlessness and chest tightness (scored 0-3), and their use of bronchodilators. Methacholine inhalation challenge tests were performed each week. Data were analysed by a method suitable for a two group, two period crossover trial with baseline measurements. 3. Terfenadine significantly reduced symptoms of cough by 76.9% (P less than 0.05) and wheeze by 46.9% (P less than 0.02). Symptoms of breathlessness and chest tightness were reduced by 16.8 and 30.3% respectively but these were not statistically significant. Morning and evening PEFR rose by 5.5 (P less than 0.001) and 6.2% (P less than 0.003) respectively on treatment with terfenadine and bronchodilator use fell by 40.3%. A progressive increase in methacholine sensitivity was seen in both treatment groups throughout the study but did not reach statistical significance. 4. We conclude that treatment with terfenadine during the grass pollen season in sensitive asthmatics reduced their symptoms and bronchodilator requirements and produced a modest improvement in their lung function without affecting the development of increased methacholine sensitivity that occurred during the grass pollen season.

Adult↗

A pseudoepidemic of Sporothrix cyanescens pneumonia occurring during renovation of a bronchoscopy suite.

Sporothrix cyanescens, an uncommonly isolated mold, was cultured from biopsy tissue, bronchial washings and sputum obtained at bronchoscopy from four patients during a one-month period. These patients had undergone fiberoptic bronchoscopy to aid in the diagnosis of pneumonic infiltrates. During this period of time the bronchoscopy suite was being extensively renovated. Cultures of bronchoscopes, biopsy forceps and effluents from the bronchoscopy injection ports were negative for fungi, as were all environmental samples taken from the bronchoscopy suite. Known pulmonary pathogens were eventually isolated from two of the patients and the pneumonias resolved in all four patients. It is believed that bronchoscopy material was contaminated by dust created during modernization of the bronchoscopy suite and that the four isolates represent a unique pseudoepidemic of S. cyanescens pneumonia.

Aged↗

Ph-negative T cells in a patient with chronic myelogenous leukemia for twenty-eight years.

The frequency of metaphases without a Philadelphia chromosome was determined in mitogen-stimulated cultures of peripheral blood mononuclear cells (PBMC) and purified T lymphocytes (93% CD2-positive) from a patient with chronic myelogenous leukemia (CML) for 28 years. The PBMC cultures contained few Ph-negative cells (8%), but they constituted 92% of the metaphases in T cell cultures, indicating few if any Ph-positive T cells in the patient's circulation. The results demonstrate that T cells derived from the leukemic clone may fail to replace the non-neoplastic population even when CML arises in childhood and the patient survives for many years. This raises questions concerning the normal role of the bone marrow as a source of T cells after infancy, and also whether Ph-positive lymphocytes may be at a disadvantage for growth.

Adult↗