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Biomedical subjects

T Bird

Publications and source records attributed to T Bird.

At least 19 recordsLinked to original sources
PubMed2026

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction ≥0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗
PubMed1992

Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder.

Amino Acid Sequence↗
PubMed1992

Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita.

Two polymorphic dinucleotide repeats--one (dGdA)n and one (dGdT)n--have been identified at the SCN4A locus, encoding the alpha-subunit of the adult skeletal muscle sodium channel. When typed using PCR, the dinucleotide repeats display 4 and 10 alleles, respectively, with a predicted heterozygosity of .81 for the combined haplotype. We have applied these polymorphisms to the investigation of hyperkalemic periodic paralysis and paramyotonia congenita, distinct neuromuscular disorders both of which are thought to involve mutation at SCN4A. Our data confirm the genetic linkage of both disorders with SCN4A. Haplotype analysis also indicates the strong likelihood of allelic heterogeneity in both disorders.

Alleles↗
PubMed1991

The mythology of threshold variations as a function of electrode surface area.

It has been established that the chronic thresholds of cardiac pacing leads vary as a function of the (spherical) electrode's radius or (geometric) surface area and the thickness of fibrotic encapsulation. Where the radius of the electrode is equal to the thickness of the fibrous capsule (about 0.7 to 1 mm for polished surfaces), threshold should be at a minimum. Where the radius of the electrode is larger or smaller than the thickness of the fibrous capsule, then thresholds should increase since the electric field strength required to stimulate decreases as the square of the distance between the electrode's surface and stimulatable tissue. In addition, it has become (incorrectly) accepted that small electrodes do not sense well. About 8-mm electrodes, therefore, became the "standard" surface area, providing the best tradeoffs between pacing and sensing. Analysis of 18 years of canine data in our laboratory, however, suggest that these relationships may be overemphasized for the surface areas of clinical interest. In fact, new small porous and steroid-eluting electrodes do not have high thresholds, are efficient, and their sensing is excellent.

Animals↗
PubMed1991

A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome.

We present a patient with a mutation in the open reading frame of the prion protein gene (PRNP), which results in substitution of valine for alanine at codon 117. The patient is a member of a large American kindred of German descent with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome (GSS). Two other affected members of this kindred carried this mutation, as inferred from haplotypes of their offspring and spouses. The mutation was absent in one member with a protracted neurologic illness that differed from the other affected members' illnesses. The identification of a distinct PRNP mutation in the telencephalic form of GSS supports the hypothesis that allelic forms of PRNP may correspond to distinct clinical disease entities.

Alanine↗
PubMed1990

A new efficient NanoTip lead.

The ideal lead has low, stable acute and chronic thresholds, high pacing impedance, and good sensing. Leads with low, stable thresholds have been developed, but pacing impedance has been in the 600 omega region. One way to increase pacing impedance is to decrease the electrode's surface area. The threshold performance and sensing ability of less than 5 mm2 electrodes have been considered questionable, up to now. We have developed a 1.5 mm2 porous, platinized, steroid-eluting electrode and have demonstrated in canine studies that it has excellent performance. Chronic thresholds are low at about 0.65 +/- 0.28 V (ventricular) and 0.42 +/- 0.12 V (atrial) at 0.5 msec. Chronic pacing impedance is in the 1200-1300 omega region, but mean chronic R and P wave source impedance is less than or equal to 1500 omega. Sensing is excellent, with almost double the P wave amplitudes usually measured in the canine.

Animals↗
PubMed1988

Circadian characteristics of dialyzable and non-dialyzable human urinary electrolytes, trace elements and total solids.

Seven clinically-healthy men ranging in age from 21 to 25 years participated in this study. Urine samples were collected at 3 hr intervals over a single 24 hr span. Urines were pooled by using 20% of the total volume collected from each subject over a 3 hr collection span. The resulting 8 pools were analyzed for pH, specific gravity, osmolality, urea N, creatine, uric acid, glucose, phosphorus, chlorides, sodium, potassium, calcium, magnesium, silicon, aluminum, zinc and total solids. Each of the 8 pools was serially dialyzed at pH 7.35 against ammonium-barbituric acid buffer. The non-dialyzable portions were then re-analyzed for the remaining solids, sodium, potassium, calcium, magnesium, silicon, aluminum and zinc. Aliquots of the non-dialyzable fraction were examined by high performance liquid chromatography. Up to twelve discernable fractions were observed in each 3 hr urine by monitoring ultraviolet light absorbance at 280 nm wavelength. Range of change throughout the 24 hr (lowest to highest value) for most variables was 100% or more. In the eight 3 hr pooled urine samples, statistically-significant circadian variation could be described for volume, pH, osmolality, urea nitrogen, creatinine, uric acid, glucose, phosphorus, chlorides, for five of eight non-dialyzed (total) components (Na, K, Ca, Si and solids) and for five of twelve non-dialyzable solid fractions, as well as for total non-dialyzable solids. Single cosinor analysis resulted in description of a significant circadian rhythm in osmolality, urea nitrogen, creatinine, glucose, phosphorus, chlorides, total Na, K, Si and solids; non-dialyzable Si and solids; dialyzable Na, K, Si and solids; and for total solids, as well as their fractions at 23.4 and 25.9 min. These observations are furnished in order to further document the extreme circadian rhythmicity in all aspects of kidney function and as reference for future work which uses any of the investigated urinary endpoints whose circadian time structure is herein described.

Adult↗
PubMed1986

Effect of heparin and heparin fractions on experimental abscess formation.

To evaluate the effectiveness of heparin and heparin fractions in decreasing abscess formation, rats were divided into six groups. A fibrin clot containing 10(9) live Escherichia coli was placed in the peritoneal cavity of each rat. Group 1 (controls) received daily subcutaneous (SQ) injections of 0.1 mL of saline solution. Group 2 received daily intramuscular injections of gentamicin, 12.5 mg/kg. Group 3 received a daily SQ dose of 30 U of porcine heparin. In addition to gentamicin, group 4 received heparin, group 5 received heparin fraction PK10169, and group 6 received heparin fraction CY216, all in daily SQ doses of 30 U. Survivors were killed at ten days and examined for intra-abdominal abscesses. All group 1 animals developed abscesses. Abscess formation was significantly decreased in all groups receiving gentamicin. When used with gentamicin, neither heparin nor heparin fractions decreased the number of abscesses formed when compared with gentamicin alone. Heparin or heparin fractions in combination with gentamicin did decrease abscess size significantly when compared with controls.

Abscess↗
PubMed1986

A common class of receptors for the two types of porcine interleukin-1 on articular chondrocytes.

IL1 causes chondrocyte-dependent degradation of the proteoglycans of the extracellular matrix of cartilage. The two types of porcine IL1 (pI5 and 8) were radiolabelled with 125I by use of the Bolton and Hunter reagent. Both labelled IL1s were fully active on cartilage. IL1/8 bound specifically to porcine articular chondrocytes. From Scatchard analysis there were calculated to be about 7,000 sites per cell with Kd 2.5 X 10(-10). All the bound radiolabelled ligand was displaceable with unlabelled IL1/8 or IL1/5 at similar concentrations. It was concluded that chondrocytes express a receptor site that reacts with either IL1.

Animals↗
PubMed1977

Malignant myelosclerosis. Myeloproliferative disorder or leukemia?

Four patients with the picture of "malignant myelosclerosis" are described and the relationship of this condition to acute granulocytic leukemia is discussed. It is suggested that there is a leukemic process from the beginning, that the fibrosis of the marrow is reactive rather than neoplastic, and that the disease should not be regarded as an accelerated form of chronic (primary) myelosclerosis. The presence of excessive reticulin in the marrow in acute leukemia, especially when the patient is first seen, indicates a bad prognosis and poor response to chemotherapy. A systemic fungal infection in one patient is described.

Adult↗
PubMed1977

A long-term follow up of patients with autoimmune thyroid disease.

A survey in a general practice in the North-East of England in 1963 detected thyroglobulin antibodies in 16.2% of women and 4.3% of men. High titres of antibodies were found in 4.6% of women and 1.6% of men. Forty six subjects with thyroglobulin antibodies (from an original total of fifty-two) were studied in 1972 and forty of these were studied further in 1975. These subjects were compared with a group of age- and sex-matched controls from the original survey. Three of the subjects had developed overt hypothyroidism by 1975 and a raised serum thyroid-stimulating hormone (TSH) concentration was found more frequently in euthyroid subjects peviously found to be antibody positive. There was a striking difference in the antibody studies in that only 26% of the previously antibody positive subjects had thyroglobulin antibodies in 1972 and 30% in 1975. A raised serum TSH concentration was found to correlate with cytoplasmic a-tibodies and particularly with the combination of cytoplasmic and thyroglobulin antibodies.

Adult↗
PubMed1977

Practolol-induced autoantibodies and their relation to oculo-cutaneous complications.

Tissue auto-antibodies were investigated in fifty-one patients (twenty-five female, twenty-six male) receiving practolol for ischaemic heart disease or dysrhythmias and compared with those found in 204 patients (fifty-eight female, 146 male) with ischaemic heart disease who did not receive practolol. Antinuclear factor (ANF) was found in 24% female and 16% male patients receiving practolol, but only in 5% of female and 4% of male patients who were not taking practolol. Thyroid cytoplasmic antibody (TCA) was detected in 16% female and 20% of male patients receiving practolol, compared to 10% of females and 6% of males in the control group. The incidence of ANF and TCA was significantly higher (P less than 0-05) in patients receiving practolol compared to the control group. The occurrence of gastric parietal cell antibody (PCA) and smooth muscle antibody (SMA) was not associated with practolol therapy (odds ratio of 2-4 and 1-9 respectively). The incidence of skin and eye complications was found to be 10% and the female to male ratio of this complication was 4 : 1. The correlation between autoantibody production and oculo-cutaneous complications could not be established in such a small group but three of the patients with the complications were found to have PCA, although PCA was found not to be associated with practolol therapy. Four of the five patients with the complications did not have circulating ANF.

Adult↗
PubMed1977

Gastric histology and its relation to anaemia in the elderly.

During 1 year 725 consecutive patients admitted to a geriatric unit were investigated for anaemia. 51% of men had haemoglobin levels below 13.5 g/dl and 41% of women had levels below 12 g/dl. 657 patients had an azuresin tubeless test meal following an augmented dose of histamine acid phosphate and 450 (68%) had achlorhydria. Gastric biopsies were performed on 240 of the patients with achloryhdria and 201 satisfactory biopsies were obtained. These were graded into five categories: (1) normal; (2) surface gastritis; (3) diffuse gastritis; (4) chronic atrophic gastritis, and (5) chronic atrophic gastritis with intestinal metaplasia. The grades of mucosal change could not be correlated with the presence or absence of anaemia, the state of gastric function as measured by the Schilling test for absorption of vitamin B12, or the level of vitamin B12 in the serum.

Achlorhydria↗
PubMed1973

Grades of hypothyroidism.

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects.Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.

Autoantibodies↗