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Biomedical subjects

J C Wade

Publications and source records attributed to J C Wade.

At least 19 recordsLinked to original sources
PubMed1998

Effects of intensive chemotherapy on bone and collagen turnover and the growth hormone axis in children with acute lymphoblastic leukemia.

To investigate the effects of disease and intensive chemotherapy on bone turnover and growth in children with acute lymphoblastic leukemia (ALL), a longitudinal prospective study was carried out in 22 children, aged 1.2-13.5 yr, enrolled in the Medical Research Council-funded randomized trial of childhood ALL treatment in the UK. We measured lower leg length and markers of bone formation [bone alkaline phosphatase (ALP) and procollagen type I C-terminal propeptide (PICP)], bone resorption [pyridinoline, deoxypyridinoline, and carboxyl-terminal telopeptide of type I collagen (ICTP)], soft tissue turnover [procollagen type III N-terminal propeptide (P3NP)], and the GH axis [IGF-I, IGF-binding protein-3 (IGFBP-3), IGFBP-2, and urinary GH] at 1- to 4-week intervals from diagnosis to week 27 of treatment. In addition, GH-binding protein was measured at diagnosis. At diagnosis, mean SD scores were: bone ALP, -1.84; PICP -1.77; pyridinoline, -1.42; deoxypyridinoline, -1.66; ICTP, -0.42; P3NP, +1.45; GH, +24.4; IGF-I, -1.70; IGFBP-3, -0.88; IGFBP-2, +2.42; and GH-binding protein, -0.69. Bone ALP, PICP, and IGFBP-3 were all correlated (P < or = 0.03). During induction and intensification, there was shrinkage of the lower leg, with decreases in PICP, pyridinoline, ICTP, and P3NP (P < 0.05), whereas IGF-I and IGFBP-3 increased (P < 0.05). After prednisolone was discontinued, bone ALP and collagen markers increased markedly (P < 0.01), but there was no significant change in IGF-I and IGFBP-3. In 12 children who received high dose i.v. methotrexate, postglucocorticoid increases in bone ALP and PICP were less, whereas those in ICTP and P3NP were greater, compared to levels in children who did not receive methotrexate (P < 0.05). We conclude that ALL itself caused GH resistance and low bone turnover. During early intensive chemotherapy, further suppression of osteoblast proliferation and osteoclast activity occurred, not mediated through the systemic GH axis, probably by the direct action of prednisolone on bone. The postglucocorticoid increase in bone turnover was also independent of the GH axis and was modulated by high dose i.v. methotrexate, which depressed osteoblast recovery and enhanced osteoclast activity.

Adolescent↗
PubMed1997

Impact of congenital or experimental hypogonadotrophism on the radiation sensitivity of the mouse ovary.

As the numbers of young people making a full recovery from haematological malignancy continue to rise, reproductive science must investigate ways of ameliorating the sterilizing effects of high-dose chemotherapy and total body irradiation. Because there is conflicting evidence as to whether lower serum gonadotrophin concentrations have any protective effect on the gonads, a study was designed to test whether either congenital or experimentally induced hypogonadism reduces the radiosensitivity of the mouse ovary. Test subjects were either homozygous for the hpg locus or animals of normal phenotype treated with a gonadotrophin-releasing hormone antagonist. At 14 days after receiving a single dose of 0.1, 0.2 or 0.3 Gy X-rays or a sham procedure, primordial follicles in the ovaries of the two experimental groups and controls were counted in serial histological sections. The doses at which half of the follicles were lost (LD50) were estimated as 0.11 +/- 0.02, 0.19 +/- 0.02 and 0.17 +/- 0.02 Gy respectively. There was no significant difference between the controls and the antagonist-treated animals, but the congenitally hypogonadal group was unexpectedly more sensitive to radiation. Either way, these results do not support the hypothesis that the ovary is protected from radiation injury by lower gonadotrophin concentrations.

Animals↗
PubMed1997

Treatment of fungal and other opportunistic infections in immunocompromised patients.

Significant improvements have been made with regard to infection-related mortality in patients with underlying immune deficiencies. Many factors predispose these patients to infection, including the incidence of profound and persistent neutropenia, but with resolution of the immune suppression the majority of these patients will survive their neutropenic period. Although most initial infections are caused by bacterial pathogens, most subsequent infections are due to fungal organisms. The mortality rate continues to be very high for immunocompromised patients who develop infection with Candida and Aspergillus. Fungal infections remain difficult to diagnose; antifungal therapy alternatives are inadequate, and these infections remain a major prevention and treatment challenge for immunocompromised patients. For the future, novel approaches that improve standard therapy, incorporate cytokines and growth factors, or focus on preventive measures offer the most effective way to deal with fungal infections.

Antifungal Agents↗
PubMed1997

Serum concentrations of carboxyl-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxyl-terminal telopeptide of type I collagen, and their interrelationships in schoolchildren.

We report pediatric age- and sex-specific 95% reference intervals for procollagen type I C-terminal propeptide (PICP), the cross-linked C-terminal telopeptide of type I collagen (ICTP), and procollagen type III N-terminal propeptide (P3NP), measured in plasma from 302 schoolchildren (156 boys, 146 girls) ages 4-19 years. All three markers displayed a significant variation with age (ANOVA P < or = 0.0015). PICP showed no detectable increase during adolescence for either sex, but decreased towards adult concentrations after the age of puberty, with an earlier decrease for girls than for boys (P < 0.01). ICTP and P3NP both increased in pubertal-aged children (P < 0.05), with an earlier increase in girls than in boys (P < 0.05), before decreasing towards adult concentrations (P < 0.01). All three collagen markers were highly correlated with one another (P < 0.001). The patterns observed mirrored the childhood growth curve and reflected the high turnover of bone and soft tissue during childhood growth.

Adolescent↗
PubMed1996

Physical therapists' perceptions of family involvement in the rehabilitation process.

The purpose of this qualitative study was to describe how physical therapists working in rehabilitation settings involved families in the patient's rehabilitation program and what factors facilitated or impeded this involvement. Forty physical therapists practicing in the eastern United States were individually interviewed on their involvement of families in a patient's rehabilitation. The interview data were transcribed, coded, and analyzed for main themes. Family involvement was found to be a significant aspect of a patient's rehabilitation. Factors pertaining to the family, the patient, the healthcare organization and the physical therapist were identified. Factors, such as the family's knowledge, attitudes and skills of the family, their relationship with the patient prior to the injury or disability, the availability and opportunity of family members to be involved, and their physical capabilities, all influenced the degree to which the family participated. Therapists also perceived the cognitive status of the patient as a factor which dictated the proper amount of family participation. The healthcare organization was an important factor which needed to encourage and support the family participation. With decreased lengths of stay there is less time for families to be independent in caring for their loved one. The organization of the department could be instrumental in this by providing multiple formal and informal avenues for family training, such as support groups, home visits, 'open door' policy visiting hours, and scheduling changes. Finally, the physical therapists might have been the single most significant factor in facilitating family involvement. It was important for them to establish open and honest communication and be pro-activists for their patients and their families. The findings were consistent with the existing literature base in relation to the patient and family. Additional findings present physical therapists and healthcare organizations with suggestions for improving family education.

Attitude of Health Personnel↗
PubMed1996

Biochemical markers of bone turnover.

Three studies to evaluate procollagen type I C-terminal propeptide, type I collagen cross-linked telopeptide and bone alkaline phosphatase (BALP) in the assessment of bone turnover and growth in children are presented. (1) In 50 short normal children treated with placebo or growth hormone, delta BALP after 3 months of treatment was highly correlated with height velocity response after 1 year (r = 0.67, p < 0.0001). (2) In 12 children with acute lymphoblastic leukaemia, marked changes in collagen peptides, BALP, and lower leg length velocity were seen during the first 6 months of chemotherapy. Suppression occurred during induction and the two intensification phases, with catch-up during the intervening phase (paired t-tests, p < 0.001). (3) Fourteen babies (birthweight < 1,500 g) treated with high-dose dexamethasone for bronchopulmonary dysplasia were compared with 25 non-steroid-treated babies < 1,500 g. Both collagen peptides decreased rapidly and dramatically (mean decreases 41-68%) after dexamethasone was started, accompanied by weight loss and lower leg shrinkage and followed by recovery during steroid weaning.

Alkaline Phosphatase↗
PubMed1994

Infections in cancer patients: some controversial issues.

Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged (more than 2 weeks) or profound (below 100 granulocytes/microliters) granulocytopenia. Agents chosen should suppress aerobic but not anaerobic flora (maintain colonization resistance) and need to have an effect on both the oral cavity and esophagus as well as the intestines.

Anti-Bacterial Agents↗
PubMed1994

Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C.

Cortical slices were prepared from the right ovaries of six lambs and either grafted directly to the ovarian pedicles of origin or cooled slowly to liquid nitrogen temperatures in medium containing dimethylsulphoxide. Three weeks later, the contra-lateral ovary was removed and replaced with frozen-thawed slices from the same animal. Two of the animals mated during their second oestrous cycle 3-4 months later and the remainder had at least one ovulatory cycle. The pregnancies reached full-term development, one lamb being derived from an ovulation in a fresh graft and the other from a frozen-thawed graft. None of the sheep had peripheral plasma concentrations of follicle stimulating hormone or luteinizing hormone consistently in the castrate range, and only one graft was devoid of follicles when the animals were slaughtered 9 months after the operations. Grafts with primordial follicles always contained developing follicles, which occasionally attained pre-ovulatory sizes of 7 mm in diameter. A corpus albicans was present in five grafts. Since all developing follicles had degenerated 1 week after grafting in an additional ewe, the large follicles in long-term grafts had presumably commenced growing after the operation. There were no obvious differences between fresh and frozen-thawed grafts in either appearance or weight, and all had apparently grown since implantation. Despite substantial depletion of primordial follicle numbers, the results indicated that frozen storage and replacement of a patient's own ovarian tissue might be practicable when fertility potential is threatened by chemotherapy/radiotherapy.

Animals↗
PubMed1993

Hickman catheters in association with intensive cancer chemotherapy.

Hickman catheters were the major venous access devices utilized at the University of Maryland Cancer Center from November 1978 to 1987. This study provided an opportunity to standardize insertion technique, to manage catheter-related activities and daily maintenance procedures in order to examine the progression of Hickman-catheter-related problems, to identify those factors that may minimize them, and to develop guidelines for the management and prevention of complications and malfunctions. In all, 690 Hickman catheters (368 double lumens) were placed in patients with acute leukemia and other cancers: 401 catheters were placed in patients with leukemia; 269 were placed during neutropenia; and 230 at platelet counts of < 50,000/microliters. Two surgeons inserted 490 catheters, and the remaining 200 were placed by a group of rotating surgeons. All catheters were placed with the intention that they would remain in place as long as clinically necessary. Total Hickman catheter days were 134273. Infectious complications included exit site infections (160), tunnel infections (46) and bacteremias (397). There were 438 instances of noninfectious complications including thrombosis, lack of function, catheter migration, fracture and hemorrhage. Recommendations for prevention and treatment of Hickman-catheter-related complications include the development of a select group committed to placement, daily maintenance and management of problems; prompt removal of catheters with Candida sp. fungemia and bacteremia due to Bacillus sp. or a bacteremia that persists for > 48 h after initiation of appropriate antibiotics, tunnel infections or Hickman-catheter-associated thrombosis. The majority of bacteremias and exit site infections can be effectively treated with antibiotics and local care.

Acute Disease↗
PubMed1993

Institutional racism: an analysis of the mental health system.

Institutional racism is defined and its conceptual application to the institution of psychiatry and the mental health system is described. Data on changes in the patient population and the provision and utilization of mental health services since deinstitutionalization are examined. Mental health policy and diagnostic and treatment issues are identified as areas in which institutional racism affects minority groups.

Deinstitutionalization↗
PubMed1993

Management of infection in patients with acute leukemia.

Substantial improvements have occurred in the infectious diseases management of patients with acute leukemia. It is now unusual for patients receiving initial induction chemotherapy at a major center to die of infectious complications without receiving an adequate course of antineoplastic treatment. Many patients also receive reinduction chemotherapy with prolonged periods of neutropenia without succumbing to major infectious complications. However, the area of management of infections in patients with acute leukemia has remained a dynamic process, with infection management issues that remain complex and controversial.

Acute Disease↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Infectious Diseases Society of America and the Food and Drug Administration.

The use of empirical antimicrobial therapy has significantly reduced the morbidity and mortality associated with untreated infections in febrile neutropenic patients. This guideline describes clinical trials of the safety and efficacy of new antimicrobial drugs in this population of patients. Fever and neutropenia should be precisely defined in each protocol. Patients should be randomized to treatment with a new or active-control drug regimen, stratified on the basis of type of cancer and age, and treated until resolution--as defined in the protocol--is attained. Outcome should be assessed both for cases with a defined microbial etiology and for those without. Final microbiological outcome is important for cases with identified pathogens, but clinical outcome is paramount.

Anti-Infective Agents↗
PubMed1992

Socialization groups: using The Book of Questions as a catalyst for interaction.

This article describes the use of The Book of Questions (Stock, 1987) as a tool for assessment and as a catalyst for social interaction in an acute short-term inpatient psychiatric unit. Examples of questions and how they can be used to provide information for the evaluation of personality style and social and interpersonal skills are provided. Group objectives, membership criteria and format, and leadership techniques are discussed. Analysis of the group activity and patients' responses to the group indicates that a group structured around The Book of Questions facilitates social interaction and is easily transferable to social activities outside of the structured therapeutic group setting and hospital environment.

Communication↗
PubMed1991

Herpes simplex virus infection in the immunocompromised cancer patient.

The development of infection remains a significant source of morbidity and mortality in the oncology patient. This patient population is at increased risk for infection because of alterations in cell-mediated immunity generated by the underlying neoplastic process and/or immunosuppressive therapy. Viral infection, particularly that attributable to herpes simplex virus (HSV), is being seen with increased frequency in the oncology patient. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. An overview of HSV infection is provided here, including discussion of the virus itself, its pathogenesis, its clinical spectrum, and current prophylactic and therapeutic approaches.

Herpes Simplex↗