Biomedical subjects

J Grill

Publications and source records attributed to J Grill.

50 records · Page 3Linked to original sources

PubMed1996

A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study.

Sixteen children with refractory or relapsed ependymoma were entered in a phase-II study of high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of busulfan 150 mg/m2/day for 4 days and thiotepa 300 mg/m2/day for the 3 following days. All patients had previously been treated by surgery and conventional chemotherapy. Eight of them had also received irradiation at doses ranging from 45 to 55 Gy at the tumor site. At the time of transplantation, 9 patients were in first relapse, 5 in second relapse and 2 in third relapse or more; all had measurable disease; 15 patients were evaluable for response. No radiologic response > 50% was observed. Stable disease and progressive disease were documented in 10 and 5 cases, respectively. The duration of response to this treatment, which lasted for a median time of 7 months (range: 5-8 months), was only evaluable in 5 patients who did not receive further treatment after ABMT. To date, there are 3 disease-free survivors at 15, 25 and 27 months all of whom were treated with second complete surgical resection and local radiotherapy (55 Gy). Toxicity was severe, mainly digestive and cutaneous, and 1 toxicity-related death occurred. Unlike medulloblastomas, ependymomas do not appear to be sensitive to this combination therapy. New therapeutic approaches are warranted.

Adolescent↗

PubMed1996

Previous conventional chemotherapy is the principal risk factor for immunoglobulin deficiency during the early post-ABMT period in children.

Humoral immunodeficiency after ABMT may worsen the course of infectious complications as already described in this clinical setting; children with low Ig values of the three isotypes during the first week after ABMT experienced more severe infections during the procedure than those with normal values. The aim of the study was to establish the prevalence, the duration and the risk factors of Ig deficiency after ABMT. Serum Ig levels of 160 children treated with high-dose chemotherapy (HDCT) followed by ABMT for solid tumors were studied prospectively before HDCT and weekly from the day after transplantation until the patients were discharged from the unit, as were the associations of the following covariates: patient characteristics, previous conventional chemotherapy (CCT), conditioning regimens, marrow graft and complications following ABMT. Serum Ig deficiency for at least one isotype was already present before HDCT in half of the children and mean serum Ig values decreased after HDCT. Serum Ig deficiency was early (day 7), inconstant, heterogeneous (IgM deficiency was more frequent and lasted longer) and brief (< 1 month). Children with low Ig values before HDCT were at high risk of profound and prolonged humoral immune deficiency. Previous CCT with more than six different drugs was the main risk factor for low serum IgM values before HDCT, on day 7 and on day 21 post-HDCT. This study shows that Ig replacement therapy could be useful after ABMT provided it is given to the patients defined on the basis of these specific risk factors and serum Ig levels before HDCT.

Adolescent↗

PubMed1995

Abnormal regional hypermethylation of the calcitonin gene in myelodysplastic syndromes.

Abnormal regional hypermethylation of the calcitonin gene can be detected in up to 95% of patients with acute nonlymphocytic leukemia (ANLL). We used a polymerase chain reaction (PCR) based assay to detect abnormal regional hypermethylation at this locus in patients with primary myelodysplastic syndromes (MDS). Hypermethylation was detected in 13 of 20 patients (65%) with MDS and was detected in nine patients with MDS and normal cytogenetics. There was no correlation between detection of this abnormality and the subtype of MDS. Four of the 13 patients (30%) with abnormal methylation have progressed to ANLL with a median time to progression of 3.5 months. The actuarial median survival of the cohort with abnormal methylation was 17 months, while that of the cohort with normal methylation is not yet reached. These preliminary findings suggest that detection of abnormal methylation at this locus may be useful as a diagnostic tool in MDS. Furthermore, hypermethylation of the calcitonin gene may be a poor prognostic feature that predicts progression to acute leukemia in patients with primary MDS.

Aged↗

PubMed1995

Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536.

Bifidobacterium species deconjugate taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, glycodeoxycholic, and glycochenodeoxycholic acids. The enzyme level increases in the growth phase. No increase in activity is observed for the cytoplasmic enzyme after addition of conjugated bile acids to a stationary-phase culture. Conjugated bile salt hydrolase (BSH) was purified from Bifidobacterium longum BB536. Its apparent molecular mass in denaturing polyacrylamide gel electrophoresis was ca. 40,000 Da. The intact enzyme had a relative molecular weight of ca. 250,000 as determined by gel filtration chromatography, suggesting that the native BSH of B. longum is probably a hexamer. The purified enzyme is active towards both glycine and taurine conjugates of cholate, deoxycholate, and chenodeoxycholate. The pH optimum is in the range of 5.5 to 6.5. A loss of BSH activity is observed after incubation at temperatures higher than 42(deg)C; at 60(deg)C, 50% of the BSH activity is lost. The importance of free sulfhydryl groups at the enzyme active center is suggested. For B. longum BB536, no significant difference in the initial rate of deconjugation and enzymatic efficiency appears between bile salts. The enzymatic efficiency is higher for B. longum BB536 than for other genera. In this paper, a new method which permits a display of BSH activity directly on polyacrylamide gels is described; this method confirms the molecular weight obtained for B. longum BB536 BSH.

Journal Article↗

PubMed1995

Selection of spirometric measurements in a clinical trial, the Lung Health Study.

Although current recommendations for spirometry require that the largest value of FEV1 and FVC should be taken from the largest values of different maneuvers, the validity of this approach was recently questioned. It has been suggested that selection of the maneuver with the largest peak flow or the maneuver with the largest FVC should be used for measurement of spirometric indices. The present analysis was therefore undertaken to determine which method of selection of spirometric maneuvers would give the least short-term variability in a clinical trial population. We examined the spirometry test sessions from 5,885 individuals with mild to moderate chronic airflow obstruction who were screened at two visits 24.9 +/- 17.1 d apart for entry into a multi-center clinical trial, the Lung Health Study. We compared eight potential selection methods for FEV1 and FVC. Using these different selection methods, the coefficient of variation ranged from 4.1 to 4.9% for FEV1 and from 3.5 to 5.7% for FVC. The average absolute difference between the two test sessions ranged from 110 to 123 ml for FEV1 and from 149 to 200 ml for FVC. Although all of the methods gave good results, the mean of the three highest values and the largest single value from all maneuvers provided the least short-term variability for both FEV1 and FVC. We therefore conclude that there is no reason to change the currently recommended selection methods for FEV1 and FVC.

Administration, Inhalation↗

PubMed1995

[Tuberculosis in children in Madagascar. 122 cases observed at the Soavinandriana-Antananarivo Hospital Center].

A group of 122 observations of pediatric tuberculosis has been studied. Nurslings represented 34% of the group, children under 8 years old 75% and only 10% were above 12. The sex ratio was 1,1. In a statistically significant way, tuberculous children were less often immunized by BCG than reference children not infected by tuberculosis. Contact has been traced back to close family in 42% of cases. Weight loss was significant at diagnosis time and after treatment the difference with the reference group disappeared. Extrapulmonary localizations were less frequent with children under 2, pulmonary and extrapulmonary localizations associations could be observed with 14% of children under 2 and with 31% of the whole children developing a proved tuberculosis. The importance of bronchial fibroscopy has been pointed out, for it allowed to detect 30% of abnormalities and to prove the diagnosis of tuberculous in 25% of cases. It is regrettable that the National Tuberculosis Control Programme did not prescribe chemoprophylaxis of contact children in its routine instructions, yet it is well known that child tuberculosis is rarely contagious and is not considered a priority by a programme. Finally, the authors reported that the number of pediatric tuberculosis managed in the country showed an obvious underestimation of the problem and they hope this work would lead to think more frequently of that diagnosis in the future.

Adolescent↗

PubMed1994

[Humoral immunity and infections during bone marrow transplantation in children: study of 127 transplanted patients successively in a same center].

BACKGROUND: Children with malignant diseases are frequently given high dose chemotherapy plus autologous bone marrow transplants. Infectious complications can lead to morbidity and mortality in this type of treatment. This study was designed to determine whether immunoglobulin deficiency is an additional risk factor for infections. PATIENTS AND METHODS: One hundred and twenty seven children with solid malignant tumors were treated between November 1987 and April 1992 in our Department by chemotherapy followed by autologous bone marrow transplantation. Their serum IgA, IgG and IgM concentrations were measured by nephelometry before chemotherapy, on the day of transplantation and every week thereafter. The frequency and severity of infectious episodes in all the children were recorded using a standard scale. The patients were divided into two subgroups, defined according to their serum IgG concentrations before the transplantation and 7 and 21 days later. RESULTS-Ig deficiency during transplantation was not associated with the occurrence of septicemia or focal infections. It was associated with the course of infection (P = 0.003) and with the occurrence of zoster virus infection during the first 6 months after transplantation (P = 0.003). CONCLUSIONS: Immune replacement during bone marrow transplantation may be indicated in children at risk of Ig deficiency. Fifty percent of the children with solid tumors treated in our institution were at risk of this deficiency.

Adolescent↗

PubMed1993

Design and results of the initial intervention program for the Lung Health Study. The Lung Health Study Research Group.

BACKGROUND: The design and results of the initial intervention program of the Lung Health Study are presented for 3,923 male and female participants. One of the major aims of this clinical trial was to achieve smoking cessation early in the study and to provide intensive follow-up procedures for maintaining abstinence. In addition, compliance with use of aerosolized inhalers (either placebo or active bronchodilator) would be necessary in order to achieve the trial goal of improved pulmonary function. RESULTS: Eighty-eight percent of the special intervention participants attended the 4-month follow-up visit. Forty-six percent reported not smoking from quit day through the visit, and an additional 13% had stopped smoking at the end of 4 months, although they had not achieved abstinence since quit day. The aerosol inhaler compliance was self-reported at 81% at the 4-month visit. Validating the self-reports by weighing canisters reduced the "good" compliance rates to 66%. CONCLUSIONS: The intensive behavioral program was effective in achieving high initial rates of smoking cessation and inhaler compliance. Use of nicotine gum appeared to be an effective adjunct to the multicomponent behavioral program. Smoking status does appear to be related to inhaler compliance among both men and women participants.

Administration, Inhalation↗

PubMed1993

[Treatment of neutropenia in Shwachman's syndrome with granulocyte growth factor (G-CSF)].

BACKGROUND: Patients with Shwachman syndrome have neutropenia and depressed neutrophil chemotaxis and are therefore susceptible to recurrent infections. The diversity of causative microbial agents makes prevention of infection difficult. Some may be life-threatening, despite antibiotic therapy and even leukocyte transfusion. PATIENT: A 15 day-old boy presented with a staphylococcal cutaneous abscess. Neutropenia was detected when he was 45 day-old and Shwachman syndrome was diagnosed at the age of 8 months. He was then suffering from pneumonia plus pancreatic insufficiency, metaphysical chondroplasia and short stature. Frequent infections continued through childhood, but became less frequent from the age of 11 years. At 17 years, he still had neutropenia (polymorphonuclear leukocytes less than 300/mm3) and profound depressed chemotaxis. He was given subcutaneous injections of recombinant human granulocytes colony stimulating factor (rhG-CSF), 1 microgram/kg/day, for 15 days. The polymorphonuclear count increased above 1000/mm3 during the second week of treatment, and this effect was seen again during a second course of rhG-CSF. The benefit was not sustained when treatment was discontinued. CONCLUSION: These results confirm earlier reports of the effect of 5 micrograms/kg/day of rhG-CSF but the responses were greater and earlier. While more precise information concerning the treatment of this disease is required, rhG-CSF can be useful in patients with severe infections.

Agranulocytosis↗

PubMed1991

Thiamine responsive anemia: report of a new case associated with a thiamine pyrophosphokinase deficiency.

We report a new case of thiamine responsive anemia in a three years old boy with the characteristic association of anemia, diabetes mellitus and deafness. Thiamine therapy corrected anemia as described. A thiamine pyrophosphokinase deficiency (TPK) was found which was not influenced by treatment. However normal levels of thiamine pyrophosphate (TPP) were obtained without correction of all symptoms particularly dyserythropoïesis. Thus, etiology of the syndrome is not only a thiamine pyrophosphokinase deficiency as previously suggested.

Abnormalities, Multiple↗

PubMed1989

Brief sexual inquiry in gynecologic practice.

Eight hundred eight-seven consecutive gynecologic outpatients were screened for sexual concerns and dysfunctions by the inclusion in the medical history of two questions concerning sexual function. Only 29 women (3%) spontaneously offered sexual complaints without direct inquiry. An additional 142 women (16%) acknowledged sexual problems upon questioning. The most common sexual complaint was dyspareunia (48%), followed by decreased sexual desire (21%), partner problem(s) or dysfunction(s) (8%), vaginismus (6%), anorgasmia (4%), and other problems (13%), eg, arousal problems, decreased lubrication, sexual anxiety, etc. Sexual complaints were more prevalent in those 50 years of age or older. This brief sexual inquiry added little time to the office visit, and most of the sexual complaints could be resolved by the gynecologist.

Adult↗

PubMed1987

Exercise in the postmenopausal woman.

Exercise merits special consideration in caring for postmenopausal women, who face both the normal physical decline accompanying aging and climacteric changes resulting from diminished ovarian function. Regular physical exercise may decrease a woman's risk of developing several medical illnesses, including osteoporosis, cardiovascular disease, obesity, and depression. Moreover, regular exercise has been shown to have a beneficial effect on flexibility, coordination, mood, and alertness. Physicians bear a special responsibility in encouraging and motivating their older patients. At this juncture in their lives, many postmenopausal women seek guidance and assistance from their doctors.

Aged↗

PubMedDate not supplied

Epidermal growth factor receptor targeting enhances adenoviral vector based suicide gene therapy of osteosarcoma.

BACKGROUND: Despite improvements in the treatment of osteosarcoma (OS) there are still too many patients who cannot benefit from current treatment modalities. Therefore, new therapeutic approaches are warranted. Here we explore the efficacy of targeted adenoviral based suicide gene therapy. METHODS AND RESULTS: Immunohistochemistry and FACS analysis detected low or absent expression levels of the primary adenovirus receptor CAR on human primary OS and human OS cell lines. These results predict a low infection efficiency and thus a reduced therapeutic effect. Targeting the adenoviruses to another receptor highly expressed on OS could overcome this limitation. We found epidermal growth factor receptor (EGFR) to be widely expressed on primary OS. Immunohistochemistry on primary tumor samples and FACS analysis on primary short-term cultures and four OS cell lines showed that EGFR was consistently expressed. The recombinant bispecific single-chain antibody 425-s11 redirects adenoviral vectors towards the EGFR. Adenovirus transduction experiments in the presence or absence of 425-s11 showed significantly enhanced gene transfer with the targeted adenoviral vector compared with the native vector (OS cell lines 2.5 to 7.2 times enhanced gene transfer and OS primary short term cultures 1.7 to 10 times enhanced gene transfer). On this basis, targeted suicide gene therapy experiments with AdCMVHSV-TK in combination with ganciclovir were performed. These experiments demonstrated up to 3.5-fold enhanced kill of OS cell lines and primary short-term cultures by the EGFR targeted vector. CONCLUSIONS: Suicide gene therapy with adenovirus targeted towards EGFR may have favorable therapeutic characteristics for future gene therapy applications in OS.

Adenoviridae↗

PubMedDate not supplied

Dactinomycin-induced, severe lichenoid eruption in a child.

There is little information in the medical literature about skin rashes associated with dactinomycin in the absence of radiotherapy. We report a 12-month-old male child who developed a severe cutaneous reaction that consisted of a widespread pruritic papular eruption associated with fever and a poor general state after dactinomycin administration. Skin biopsy specimen findings confirmed the diagnosis of lichenoid eruption. The rash improved with topical steroid treatment and completely resolved within 1 month with persistence of a residual mild hyperpigmentation. Dactinomycin administration was discontinued for the remaining cycles of chemotherapy.

Antibiotics, Antineoplastic↗