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Biomedical subjects

J Gray

Publications and source records attributed to J Gray.

At least 217 records · Page 12Linked to original sources

Illness induction syndrome: paper I--a series of 41 children from 37 families identified at The Great Ormond Street Hospital for Children NHS Trust.

At the hospital 41 children from 37 families were identified as having had illness induced by a parent who in all but three cases was the mother. Their case records were reviewed. Four patterns of presentation occurred; failure-to-thrive through the active withholding of food; allegation of allergy and withholding of food; allegation and fabrication of medical symptoms; and active interference by poisoning or disrupting medical treatment. Four of the children died, two as a result of the illness induction. In 35% of the families a sibling had been previously subjected to some type of abuse. All the children had been presented with potentially serious symptoms, but post-identification only five were found to have serious medical problems requiring ongoing treatment. There were no specific characteristics of either the child or family associated with each type of presentation. Seventeen children had previously presented with failure-to-thrive, feeding problems or food allergies. All the mothers had suffered at least one of the following: privation, child abuse, psychiatric illness, or significant loss or bereavement, whereas only half the fathers had grown up in a deprived family situation and/or had earlier or current health difficulties. Forty percent of the parents had serious marital problems. A combined medical/psychosocial team identified the abuse and attempted to understand the family's belief system regarding the illness. The process of Illness Induction was conceptualized as being initiated by the parents perceiving the child to be ill and using this focus on illness as a way of solving major personal, marital, and/or family difficulties.

Child, Preschool↗

Selective neck dissection and the management of the node-positive neck.

OBJECTIVE: To assess the oncologic effectiveness of the selective neck dissection (SND) in patients with both clinically and pathologically proven regional metastases. METHODS: A 4-year retrospective medical chart review was conducted in an academic tertiary care referral center. Twenty-nine patients with a newly diagnosed upper aerodigestive tract squamous cell carcinoma, and both clinically and histologically proven cervical metastases who underwent 36 SND, had their records reviewed. Minimum follow-up was 2 years. RESULTS: Regional metastasis were staged N1 in 13 patients, N2A in 1, N2B in 8, and N2C in 7. Seventeen supraomohyoid and 19 lateral neck dissections were performed. Extracapsular spread of tumor was present in 11 patients. Postoperative radiation therapy was administered to 20 patients. Actuarial disease-specific survival at 4 years was 47% overall, 67% in N1 patients, and 41% in N2 patients. Only 1 failure in the treated neck occurred for a 4-year actuarial regional failure rate of 4%. The actuarial local failure and distant metastasis rate were 36% each. CONCLUSIONS: In carefully selected patients with clinically and histologically apparent regional metastases, the selective neck dissection can be an oncologically effective procedure.

Adult↗

A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22.

The population prevalence of multiple sclerosis is 0.1%; however, the risk of the disease in the siblings of affected individuals is very much higher at 3-5%. The importance of genetic factors in accounting for this increased risk is confirmed by the results of twin and adoption studies. Despite the evidence for a strong genetic effect, a weak major histocompatibility complex (MHC) association is the only consistently observed feature in the genetics of multiple sclerosis. Other candidates have been proposed, including genes encoding the immunoglobulin heavy chain, T cell receptor beta chain and APOC2, but none has yet been confirmed. Evidence for linkage and association to the myelin basic protein gene has been reported in a genetically isolated Finnish population, but it has not been possible to reproduce these results in other populations. We used a two-stage approach to search the human genome for the genes causing susceptibility to multiple sclerosis. Two principal regions of linkage are identified, chromosomes 17q22 and 6p21 (MHC). Our results are compatible with genetic models involving epistatic interaction between these and several additional genes.

Chromosome Mapping↗

The micro-laserbot: an alternative method for frameless stereotactic localization.

An alternative method for frameless stereotactic localization which combines an articulating arm for spatial positioning with a three-dimensional laser beam localization technique will be presented. The moveable segments of the arm are counterbalanced, and allow it to smoothly glide to a given position. Micro-brakes in the arm joints permit rigid spatial fixation. The proximal end of the micro-laserbot attaches to the operating room table and the distal end, with the laser localizer apparatus, can be either free or attached to the operating microscope around the objective lens assembly. When attached to the surgical microscope, the laser light beams projected on the brain surface are seen while viewing the surgical field through the operating microscope. When used in this mode, the standard surgical microscope is converted into a stereotactic positional device, and the lasers guide the surgeon during the surgical dissection. Intersection of the laser beams indicate the spatial position of targets and volumes which are referenced and seen on the multi-modality computer imaging system. When not attached to the microscope, various other instruments can be affixed to the distal end of the micro-laserbot for stereotactic referencing.

Equipment Design↗

Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.

PURPOSE: A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS: Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS: Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION: This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.

Adult↗

The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil.

BACKGROUND: Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, central alpha-agonists, and other vasodilators. Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal. METHODS: A three-phase, randomized, double-blind, placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension. After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride, patients received ibuprofen, naproxen, or placebo matching capsules for 3 weeks, and blood pressure, heart rate, weight, and adverse effects were evaluated. A general linear model with 95% confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group. RESULTS: No significant differences in sitting, standing, or supine blood pressure were noted with naproxen or ibuprofen compared with placebo. The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar. Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies. Changes in pulse rate were not significant. The incidence of adverse effects was similar across all three treatment groups. CONCLUSIONS: The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure. Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy.

Adolescent↗

Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability.

By crossing mice that carry a null allele of p53 with transgenic mice that develop mammary adenocarcinomas under the influence of a Wnt-1 transgene, we have studied the consequences of p53 deficiency in mammary gland neoplasia. In Wnt-1 transgenic mice homozygous for the p53 null allele, tumors appear at an earlier age than in animals heterozygous or wild-type at the p53 locus. About half of the tumors arising in p53 heterozygotes exhibit loss of the normal p53 allele, implying selection for p53-deficient cells. Mammary tumors lacking p53 display less fibrotic histopathology and increased genomic instability with aneuploidy, amplifications, and deletions, as detected by karyotype analysis and comparative genomic hybridization. In one tumor, the amplified region of chromosome 7 had an ectopically expressed int-2/FGF3 proto-oncogene, a gene known to cooperate with Wnt-1 in the production of mammary tumors. These findings favor a model in which p53 deficiency relaxes normal restraints on chromosomal number and organization during tumorigenesis.

Adenocarcinoma↗

Chromosomal localization of the gamma-glutamyl carboxylase gene at 2p12.

We have used two complementary approaches to analyze the chromosomal location of the gamma-glutamyl carboxylase gene. The amplification of a carboxylase-specific genomic fragment by polymerase chain reaction (PCR) in a human-rodent hybrid cell mapping panel localized the gene to chromosome 2. Mapping by fluorescence in situ hybridization assigned the gene to p12 of chromosome 2. Our results indicate that the gamma-glutamyl carboxylase gene has a single locus in the human genome.

Animals↗

Life expectancy in the Marfan syndrome.

Data reported in 1972 indicated that lifespan in patients with the Marfan syndrome is markedly shortened, and that most deaths are cardiovascular. This study was performed to determine whether survival in the Marfan syndrome has changed since 1972, and to discern whether treatment (medical or surgical) has altered prognosis. Survival curves were generated on 417 patients from 4 referral centers, with a definite diagnosis of the Marfan syndrome. Birth date, age at death, cardiovascular surgery, or treatment with beta blockers, or any combination of these, were included in the analysis. Forty-seven of 417 patients died. Mean age at death (41 +/- 18 years) was significantly increased compared with age in 1972 (32 +/- 16 years, p = 0.0023). Median (50%) cumulative probability of survival in 1993 was 72 years compared with 48 years in 1972. Of 112 surgically treated patients, 10-year probability of survival was 70%. Patients undergoing surgery after 1980 enjoyed significantly increased survival than patients who had undergone operation before 1980 (p = 0.008). In conclusion, life expectancy for patients with the Marfan syndrome has increased > 25% since 1972. Reasons for this dramatic increase may include (1) an overall improvement in population life expectancy, (2) benefits arising from cardiovascular surgery, and (3) greater proportion of milder cases due to increased frequency of diagnosis. Medical therapy (including beta blockers) was also associated with an increase in probable survival.

Adult↗

A therapeutic preschool for abused children: the KEEPSAFE Project. Kempe Early Education Project Serving Abused Families.

Twenty-four children attended a therapeutic preschool for physically and sexually abused children, the Kempe Early Education Project Serving Abused Families (KEEPSAFE), over a 3-year period from 1985-1988. The program provided early education and therapy for abused children so that they could improve developmentally, socially, and emotionally, with the aim that the children would be suitable to enter the public education system. The therapeutic preschool was combined with a home visitation program for the child's parents or primary caretaker, focusing on improving the quality of interaction between the adult and child. The majority of children made developmental gains at a faster rate than would normally be expected as measured by the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test. Although all 24 children were thought at onset of intervention to be unable to participate in a public school setting, after 12 months in the program over 79% were staffed into the public school system eight (33.3%) into a regular classroom. Three others (12.5%) needed residential care, and two were too young to enter public school. Even though a therapeutic preschool is expensive in terms of the high staff to child ratio needed, it is likely to be beneficial in improving the developmental skills of abused children.

Child Abuse↗

Non-enteritic aeromonas infections in hospitalized patients.

Aeromonas species were isolated from specimens other than faeces from 59 hospital inpatients over a 15 year period. Of the isolates, 79.7% were regarded as clinically significant, with skin and soft tissues and blood cultures as the commonest sites of infection. Of the isolates, 52.5% were hospital-acquired, and 55.9% of patients had serious underlying disease. Community-acquired infections in previously healthy individuals accounted for only 13.6% of isolates. However unlike many other opportunistic infections, aeromonas infection was not closely associated with prior antibiotic therapy, nor was there a significant increase in the frequency of infection over the study period.

Adolescent↗

Carboxyfluorescein and biotin neuromedin C analogues: synthesis and applications.

Two neuromedin C (NC) analogues were constructed by Fmoc synthesis and in situ coupling of 4(5)-carboxyfluorescein or biotin to the N-terminus. Both displayed full agonism in an amylase release assay and cross-reacted fully with a NC-specific antiserum. Biotin NC functioned in a streptavidin-capture ELISA. Carboxyfluorescein NC was used to probe receptor localization in rat stomach. Specific NC binding sites, which did not interact with substance P, angiotensin I, or neurokinin A, were labeled in the antrum. Identity of NC binding sites was confirmed by microautoradiography. The specifically labeled cells were all found in the lamina propria and at least some of cells were identified as eosinophils.

Amylases↗

Family history of severe cardiovascular disease in Marfan syndrome is associated with increased aortic diameter and decreased survival.

OBJECTIVES: We attempted to determine whether a family history of severe cardiovascular disease in patients with the Marfan syndrome is associated with increased aortic dilation or decreased survival, or both. BACKGROUND: The prognostic importance of a family history of severe cardiovascular disease in patients with the Marfan syndrome has been incompletely examined. We hypothesized that such a family history would correlate with increased aortic dilation and would be associated with decreased survival. METHODS: One hundred eight affected patients and 48 unaffected family members from 33 multigenerational families with the Marfan syndrome underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at death ascertained from family pedigrees were used to perform life table analysis and estimate survival. RESULTS: Aortic root and arch diameters were significantly greater in patients with a family history of severe cardiovascular disease than in patients without such a family history. Of subjects in the highest quartile for aortic size, > 80% had such a family history in contrast to < 10% of those in the lowest quartile (chi-square 57.37, p < 0.00001). Mean age at death and cumulative probability of survival were significantly lower in patients with such a family history. CONCLUSIONS: Among patients with the Marfan syndrome, aortic dilation is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in patients with the Marfan syndrome.

Adult↗