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Biomedical subjects

T C Brown

Publications and source records attributed to T C Brown.

At least 73 records · Page 4Linked to original sources

Patterns of disease in localized extranodal lymphomas.

The site of origin of lymphoid tissue is an important determinant of lymphocyte migration patterns. The association of gastrointestinal (GI) and Waldeyer's ring lymphoma and the unique lymphocyte migration pattern of gut-associated lymphoid tissue (GALT) have been previously described. To establish whether predictive clinical patterns of disease occur in localized Non-Hodgkin's lymphoma, survival and relapse patterns for 496 patients with stage I and II non-Hodgkin's lymphoma (NHL) treated with loco-regional irradiation (XRT) alone were examined. We identified 139 patients with GALT lymphoma (defined as arising from primitive gut and including Waldeyers' ring, thyroid, and GI lymphomas) and 87 patients with extranodal non-gut-associated lymphoma (ENL). Survival and relapse data were assessed in multifactorial analysis to correct for previously identified other prognostic variables. GALT lymphomas (GALT-L) have a survival advantage compared with other ENL (P = .017) independent of stage and histology. A difference in distant relapse (DR) rate between GALT-L and other ENL (P = .0002) was also identified. The presentation site of localized extranodal NHL is predictive of clinical behavior and is an independent determinant of outcome. This may be an expression of lymphocytic origin and determinants of migration patterns.

Abdominal Neoplasms↗

Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men.

Cells from the anorectal mucosa of 61 homosexual men were examined microscopically for evidence of papillomavirus infection and dysplastic changes. There was cytological evidence of dysplasia with concomitant features of human papillomavirus (HPV) infection on at least one occasion in 24 men and of papillomavirus infection without dysplasia on at least one occasion in a further 26: dysplasia was present for over one year in 9 of 14 men who were re-examined. Dysplasia was associated with a history of anal warts, frequent receptive anal intercourse, presence of serum antibody to human immunodeficiency virus (HIV), and immune dysfunction as judged by a low CD4/CD8 ratio, but not with the lifetime number of sexual partners. The association of longlasting dysplasia with anti-HIV was independent of the association with immune dysfunction. Thus infection of anorectal mucosal cells with papillomavirus seems to be frequent among homosexual men and may predispose to dysplasia.

Acquired Immunodeficiency Syndrome↗

DNA of human Raji target cells is damaged upon lymphocyte-mediated lysis.

Human Raji target cells DNA is degraded by the introduction of single-strand breaks (alkali-sensitive sites) upon lymphocyte-mediated lysis. This type of DNA degradation appears earlier and is more extensive in lymphocyte-than in antibody + complement-mediated lysis of Raji cells, regardless of the species of effector lymphocytes (human or mouse). Mouse P815 target cell DNA is extensively fragmented (yielding 200 base pair fragments) when human or mouse lymphocytes are used to lyse P815. Thus, these observations indicate that both human and mouse target cell DNA are affected during lymphocyte-mediated lysis. Moreover, the pattern of DNA degradation in target cells lysed by effector lymphocytes is characteristic of the target cell species, suggesting that DNA degradation proceeds through the activation of target cell endonuclease(s).

Animals↗

Ultraviolet radiation inactivates SV40 by disrupting at least four genetic functions.

We have examined the relative sensitivities of different genetic functions to damage induced by u.v. light. For this purpose we have introduced defined amounts of damage into specific regions of the genome of SV40 and have determined the effect of the damage on the survival of transfected viral DNA. We found that the lethal effect of the damage depends on its location within the viral genome. The region most sensitive to damage contains the transcriptional promotors and enhancers for the early and late viral genes plus part of the origin of DNA replication. Lesions within this regulatory region are 3.2-fold more effective in inactivating viral DNA than is the same amount of damage randomly distributed throughout the viral genome. The region least sensitive to damage lies within the coding portion of the viral coat protein genes, which are expressed only late in infection and would therefore be transcribed from undamaged progeny viral genomes, provided DNA replication occurs. Damage within this region is only 45% as effective in inactivating viral DNA as are randomly distributed lesions. Thus there is a 7-fold difference in the lethal effect of DNA damage within the most sensitive and least sensitive regions of the viral genome. Intermediate sensitivities are observed within the transcribed portion of the viral A gene, coding for the T antigen whose expression is required early in infection, and in a region at the terminus of DNA replication. The sum of the individual sensitivities for all regions of the SV40 genome is equal to the total sensitivity of viral DNA subjected to random damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A new approach to lateral cutaneous nerve of thigh block.

A new approach to the lateral cutaneous nerve of thigh is described. It depends on locating the depth of the canal through which the nerve passes immediately medial to the anterior superior iliac spine. Anatomical dissections show that it lies deep to the attachments of external oblique aponeurosis, the internal oblique muscle, and a deep fascial layer. Two district 'pops' or loss of resistance can be identified during insertion of a short-bevelled needle. Location of the canal by the technique described has been confirmed radiographically.

Anesthesia, Local↗

Plasma bupivacaine concentrations following lumbar epidural anaesthesia in children.

Plasma levels of bupivacaine were measured following lumbar epidural administration of 3 mg/kg of 0.5% plain solution in sixteen children. The peak levels were generally between 1.0 and 2 micrograms/ml, the highest being 2.9 micrograms/ml. No manifestations of toxicity were observed. There was a significant positive correlation between peak plasma levels and increasing age.

Aging↗

The influence of age on lignocaine pharmacokinetics in young puppies.

Eight mongrel puppies were studied at intervals of a few weeks. Lignocaine 4 mg/kg was infused over 60 seconds. Frequent samples were taken over 30 minutes for plasma lignocaine assay. Initially the concentrations were significantly higher in the oldest group (178-191 days) but after 10 minutes the youngest group (3-16 days) had significantly higher levels than the other groups. Pharmacokinetic data derived included the rate constants k21, k12 (drug movement between two compartments), k10 (elimination from the central compartment), and the volume of distribution (V beta). The elimination rate constant k10 was significantly lower in Group 1 (3-16 days) than all other groups and Group 2 (37-57 days) was lower than Group 4 (178-191 days). The calculated beta half-life was significantly longer in the youngest group than the others. There was no significant difference in the volume of distribution between these age groups--up to 6 months.

Aging↗

An approach to posterior femoral cutaneous nerve block.

An approach to blocking the posterior femoral cutaneous nerve at the point where its branches emerge from below the medial border of gluteus maximus is described. This is located by inserting the needle at a point one quarter of the distance from the ischial tuberosity to the greater trochanter in the gluteal fold and then feeling two distinct losses of resistance as superficial and deep fascia are penetrated with a short-bevelled needle.

Humans↗

Role of radiation therapy in localized non-Hodgkin's lymphoma.

Relapse occurs in 50% of patients receiving radiation for clinical stage (C.S.) I and II nodal and extranodal non-Hodgkin's lymphoma (N.H.L.). Prior to the introduction of intensive chemotherapy those failing primary control with irradiation and most of those who relapsed died of their disease with a resultant overall mortality of 50%. An analysis of Princess Margaret Hospital results with radiation for C.S. I and II N.H.L. between January 1967 and December 1978 revealed that tumour bulk, age, stage and histology were of independent prognostic significance. It was possible to group patients using combinations of these attributes so that each group encompassed only patients with similar outcomes. Such prognostic groups were identified separately within the low grade and the intermediate plus high grade categories of the Working Formulation. Patients with a high probability of cure with radiation were so defined. Also those patients in whom chemotherapy would be optimal initial therapy were also defined. Such patients were in the intermediate plus high grade histology groups. Thirty percent of all patients with low grade histology lymphoma had an actuarial survival of 83%, and relapse-free rate of 63% at 10 years. By implication, approximately 20% of all patients with these histologies seen at the Princess Margaret Hospital for the same time period achieved prolonged relapse-free survival by localized therapy. This is at variance with the implications of staging from studies where laparotomy and multiple bone marrow biopsies have been used. Such aggressive staging procedures suggest truly localised disease in only 5-6% of patients with low grade lymphoma. A significant relationship between radiation dose and disease control was demonstrated only for patients with intermediate and high grade lymphoma of medium or large bulk. A minimum tumour dose of 30 Gy was required for optimal local control with radiation.

Adult↗

Poly ADP-ribosylation and DNA strand breakage in SV40 minichromosomes.

Poly ADP-ribosylation and DNA strand breakage in response to treatment with the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were studied on SV40 minichromosomes in SV40-infected, permeabilized CV-1 monkey cells. After an initial sharp increase in poly ADP-ribosylation, strand breakage and poly ADPR increased proportionately with increasing dose of MNNG. This suggests a cause-effect relationship between the two reactions. The major poly ADP-ribose acceptor of minichromosomes was core histone H2B. In contrast, H2B, H2A, H1 and protein A24 were poly ADP-ribosylated in the nuclear chromatin of the same cells.

Animals↗

Drug overdose in children.

This paper reviews epidemiological factors, drugs taken, management and outcome of 478 children admitted to the Royal Children's Hospital with drug poisoning during the 5 years 1978-82. Accidental ingestion in young children is still common whilst self poisoning is increasing in the age group 8-17 years. Suicide attempts and self destructive ingestion accounted for 11.5% of all cases with two deaths. A significant number in this group were less than 10 years of age. Iatrogenic poisoning accounted for 11% of all cases with metoclopramide or prochlorperazine frequently involved. Benzodiazepines, major tranquillizers and antihistamines were the most commonly taken groups of drugs whilst the greatest number of admissions to Intensive Care Unit were due to tricyclic poisoning. Principles of management are discussed.

Accidents↗

A comparison of different concentrations of lignocaine hydrochloride used for topical anaesthesia of the larynx of the cat.

Electromyographic (EMG) recordings were made from the intrinsic laryngeal muscles (cricothyroid, thyroarytenoid) and the diaphragm of the cat to compare the effect of the same dose of different concentrations of lignocaine hydrocholoride applied topically to the laryngeal mucosa. All concentrations of lignocaine hydrochloride tested, two, five and ten per cent, produced desensitisation of the larynx, as demonstrated by a loss of response of the crocothyroid and thyroarytenoid to mechanical stimulation of the mucosa. Desensitisation was produced in a mean of 1.80 minutes in the thirty experiments performed. Return of baseline response took significantly longer when 5 or 10% lignocaine was used compared with that when 2% was used (p less than 0.05). The usefulness of lignocaine hydrochloride as a topical anaesthetic for the larynx is reviewed.

Anesthesia, Local↗

Temperature maintenance in infants undergoing anaesthesia and surgery.

A study has been conducted on infants under six months of age during induction and anaesthesia to compare the effect on heat loss when a warming blanket, a humidifier and an overhead heater were used. The combination of all three was associated with significantly less heat loss than when the blanket was used alone. The particular benefit of the overhead heater during prolonged preparation for neurosurgery was also demonstrated. It is recommended that overhead heaters should be used during induction of anaesthesia in infants.

Anesthesia↗

The influence of age on plasma lignocaine levels following tracheal spray in young dogs.

A study was conducted in puppies of one litter beginning before they were three weeks old and repeated up to six times in the first four months of life to determine whether any age-related changes in peak plasma lignocaine levels occurred following tracheal spray. These were significantly higher in the youngest group (less than 20 days) than in dogs 2-3 months of age. There was a significant negative correlation between peak plasma levels and age up to four months. The maximum level attained by any puppy was 4.48 ug/ml after 4 mg/kg tracheal lignocaine spray.

Aerosols↗