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Biomedical subjects

S Wikström

Publications and source records attributed to S Wikström.

At least 19 recordsLinked to original sources

Cell-based multiwell assays for the detection of substrate accumulation and oxidation.

We describe multiwell assays for detecting the accumulation as well as the subsequent oxidation of (14)C-labeled substrates in cultured cells. Accumulation is monitored in real time by an established scintillation proximity assay in which the scintillator is embedded in the plate base primarily detecting cell-associated radiolabel. The substrate oxidation assay is a novel variant of previously described experimental approaches aimed at trapping (14)CO(2) produced by isolated enzymes, organelles, or intact cells. This method uses a standard 96-well tissue culture plate and, on top, an inverted filter plate immersed with NaOH that are clamped into a sandwich sealed with a silicon gasket to obtain gas-tight compartments. (14)CO(2) is captured in the filter and quantified by conventional scintillation. We demonstrate both the accumulation and subsequent oxidation of (14)C-labeled substrates in cultured human myotubes, adipocytes, and hepatocytes. Both methods are adaptable for compound screening; at the same time, these protocols provide easy-to-use and time- saving methods for in vitro studies of cellular fuel handling.

Adipocytes↗

Attitudes about dental care among parents whose children suffer from severe congenital heart disease: a case-control study.

OBJECTIVES: To examine attitudes and experiences of parents whose children have complex congenital heart disease (CHD) with respect to dental health information and advice, dental care, and service and to compare the results with data from an age- and gender-matched control group without any medical problems. SETTING: Faculty of Medicine (Paediatric Cardiology and Paediatric Dentistry), Umeå University, Umeå, Sweden. SAMPLE AND METHOD: Each group comprised parents of 33 children; the children's mean age was 9.4 years. All the cases and the controls resided in the county of Västerbotten, northern Sweden. Data were collected with a questionnaire with 20 joint questions to both groups and four additional questions to the CHD group. RESULTS: Of the 20 joint questions, significant differences were displayed in the following areas: the professional group that provided the parents with dental health information and advice (P < 0.01), attitudes to reception at the dental clinic, and experience of sedation before operative dental treatment (P < 0.05). Parents to 11 children with CHD who were patients at a specialist clinic for paediatric dentistry scored the reception at the dental clinic as excellent in nine cases and satisfactory in two, compared to excellent (3), satisfactory (11), decent (4), and poor (4) among those who were patients in general dental practice (P < 0.01). No statistically significant differences in educational level or in parental experience of dental health were noted between the two groups (P > 0.05). CONCLUSION: Children with CHD in northern Sweden mainly receive their dental health information from a physician or a dentist, and healthy children mainly receive information from a dental hygienist indicating that children with CHD are given priority in the dental care system. Parental attitudes to reception in the dental service differed, and parents of healthy children scored the reception at the dental clinic better than parents of children with CHD. It is suggested that children with severe CHD should receive dental care in clinics for paediatric dentistry, particularly at early ages.

Adolescent↗

Growth patterns in young men treated for undescended testes in childhood.

Testicular maldescent may be caused by endocrinological deficiency in some cases, and, on the other hand, cryptorchidism itself may have an injurious effect on testicular development and function. The purpose was to examine whether testicular maldescent is associated with abnormal growth in various body dimensions in otherwise healthy males treated for the malformation during childhood. A total of 76 young men, 16-30 years of age, who were treated for undescended testes at an age ranging from 10 months to 13 years, were examined by measuring various body dimensions. Previously cryptorchid men were slightly taller than age-matched controls, except for those with bilateral cryptorchidism treated preoperatively with hCG. The most prominent finding was a high bihumeral to bicristal ratio. In addition, testicular volume was positively correlated to both the bicristal and bihumeral width, as well as to the sitting and total height.

Adolescent↗

Tactile stimulus and neurohormonal response: a pilot study.

The effects of tactile stimuli on plasma oxytocin and neuropeptide Y (NPY) were investigated in 21 volunteers exposed to massage. Blood samples for basal values were drawn immediately before and immediately after finishing the massage. A third sample was drawn after 60 min of restricted rest. On focusing on the difference between oxytocin concentrations before and immediately after massage, we found a sex difference. An opposite sex difference was found for NPY. The results imply that there might be sex-related difference in neurohormonal response to tactile stimuli such as in massage, and the results contradict those of previously reported animal experiments.

Adult↗

Comparative genomic hybridization reveals changes in DNA-copy number in poor-risk neuroblastoma.

Aggressive neuroblastoma remains a therapeutic challenge, and additional understanding of its biology is of paramount importance. Changes in DNA-copy number were analysed in the neuroblastoma cells of 27 patients using comparative genomic hybridization (CGH). Eighteen of the patients had a poor risk disease (16/18 stage IV) and 9 had a non-poor-risk disease (3/9 stage I-II, 2/9 stage III, and 4/9 stage IVS). Changes in DNA-copy number were detected in 72% of the poor-risk and 22% of the non-poor-risk tumors with gains of chromosomal material being more prevalent than losses. Gains were most common in chromosomes 2, 7, and 17 and losses in chromosome 11. Changes in DNA-copy number were multiple in all but one of the patients with poor-risk disease. The applicability of CGH in studies on the genomic changes in pediatric malignancies is demonstrated by our data also adding weight to the argument of multiple elements with oncogenic and/or tumor suppressor potential being involved in the aggressive phenotype of poor-risk neuroblastoma.

Aneuploidy↗

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND: Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS: A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS: Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS: Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.

Acute Disease↗

Predominance of class II papG allele of Escherichia coli in pyelonephritis in infants with normal urinary tract anatomy.

P-fimbrial genotypes of Escherichia coli strains and their possible association with urinary tract abnormalities were studied in infants with pyelonephritis. A total of 153 urinary E. coli strains were analyzed by polymerase chain reaction for class I, II, and III alleles of the pyelonephritis-associated adhesin gene papG. Strains with any class II papG alleles were found significantly more often in infants with normal anatomy and function or in infants with clinically insignificant abnormalities than they were in infants with significant abnormalities (90 of 119 vs. 14 of 34 infants; P<. 001). On the other hand, strains without any papG alleles were found significantly more often in infants with major urinary tract abnormalities (11 of 34 vs. 17 of 119 infants; P=.016). Our genotypic findings indicate that, especially in infants with a normal urinary tract, infection is caused by more-virulent E. coli than is present in infants without a normal urinary tract. This virulence could be due to expression of pyelonephritogenic P fimbriae by an infecting E. coli strain.

Adhesins, Escherichia coli↗

Maximal preservation of renal function in patients with bilateral Wilms' tumor: therapeutic strategy of late kidney-sparing surgery and replacement of radiotherapy by high-dose melphalan and stem cell rescue.

In children with bilateral Wilms' tumor, the therapy should aim at maximal preservation of renal parenchyma and function. Local radiotherapy may give rise to second malignant neoplasms and may impair renal function. We present a therapeutic strategy without any irradiation. Three children were diagnosed with bilateral Wilms' tumor at ages from 6 months to 5 years. Each patient had a massive tumor with local stage III on one side; one had pulmonary metastases. The therapeutic strategy was first to obtain tissue for histology by percutaneous needle biopsy, to administer pre-operative chemotherapy until desired tumor shrinkage, and then to perform kidney-sparing resective surgery. After a period of conventional chemotherapy, the patients were consolidated with high-dose (HD) melphalan and ABMT. Renal parenchyma spared post-surgery (right/left) was 0%/70%, 60%/40% and 40%/60% of the original kidney volumes. The toxicity of the ABMT procedure was mild, the patients engrafted promptly, and were discharged on days +14 to +27. All patients survive disease-free, 3 years 4 months to 4 years 5 months post-transplant. Our program resulted in good preservation of renal parenchyma and normal function, and we consider the risk of this ABMT program smaller than the late consequences of local radiotherapy for children with bilateral Wilms' tumor. The therapeutic strategy described merits further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult.

Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment.

Adult↗

Sexual development in patients treated for cryptorchidism.

An analysis of sexual development was carried out in adult patients treated in childhood for cryptorchidism. Forty-seven healthy men served as a control group. The cryptorchid patients had been treated between the ages of 10 months to 13 years and their ages ranged from 16 to 30 years at follow-up. The onset of puberty, and sexual development, were within normal limits in all patients, although spermarche occurred somewhat later in the patients than in the controls. In addition, the patients were on average slightly less sexually active than the controls. Neither age at the time of treatment nor the method of treatment correlated with current sexual activity. The patients with larger testes were, however, sexually more active. Both treatment age and the method of treatment, whether hormonal or surgical, should be selected on the basis of fertility prognosis.

Adolescent↗

Are repeated desmopressin treatment attempts successful?

The efficacy of repeated treatment attempts using desmopressin (Minirin, DDAVP), either alone, alternately or in combination with an alarm device, were evaluated in 96 patients with primary nocturnal enuresis who were slow, delayed or non-responders to therapy. At follow-up, 52% of the patients were cured and off therapy, an additional 26% had achieved dryness when using desmopressin regularly or on special occasions, and 22% were still wetting. It can be concluded that desmopressin therapy can be successfully commenced at the age of 5 years. Repeated treatment attempts can lead to achievement of dryness at an earlier stage. However, they probably do not influence the final outcome.

Administration, Intranasal↗

Effect of age at operation, location of testis and preoperative hormonal treatment on testicular growth after cryptorchidism.

PURPOSE: We evaluated the effect of patient age, primary location of the gonad and preoperative human chorionic gonadotropin administration on future testicular growth in patients treated for cryptorchidism. MATERIALS AND METHODS: Testicular volume was measured in 75 adults treated for cryptorchidism when they were 10 months to 13 years old. RESULTS: The mean volume of the cryptorchid testes plus or minus standard deviation, whether unilateral or bilateral, was 11 +/- 6 ml. compared to 20 +/- 7 ml. for the spontaneously descended testes in patients with unilateral cryptorchidism. The results showed no significant correlation between patient age at treatment or original testicular location and final testicular volume, although the 22 testes of 18 patients undergoing surgery after age 5 years were somewhat smaller (9 +/- 5 ml.) than the 66 testes of 55 younger patients (12 +/- 6 ml.). However, 26 patients who had received human chorionic gonadotropin treatment had a significantly smaller testis (9 +/- 5 ml.) than did 57 treated with surgery alone (12 +/- 6 ml., p < 0.05). CONCLUSIONS: Early orchiopexy at age younger than 2 years is not necessarily essential. Adult testicular volume is slightly greater in patients with cryptorchidism if treated at ages up to 5 years. Preoperative location of the testis in otherwise healthy boys exerts no definite effect on final testicular volume. Preoperative human chorionic gonadotropin administration may have an adverse effect on future testicular growth.

Adolescent↗

Ultrasonography and colour Doppler flow in the testes of adult patients after treatment of cryptorchidism.

OBJECTIVE: To analyse the prevalence of post-operative structural, parenchymal and vascular testicular abnormalities and the incidence of epididymal abnormalities in adult men treated for undescended testes in childhood. PATIENTS AND METHODS: The testes and epididymi of 76 adult men treated for cryptorchidism in childhood were evaluated 16 to 27 years after treatment, using colour Doppler ultrasonography. RESULTS: The 61 spontaneously descended testes were significantly (P < 0.01) larger (mean [SD], 22 [8] mL) than the 90 undescended testes (13 [6] mL). The echo pattern in all the spontaneously descended testes was normal, whereas in 15 cases (17%) the testicular tissue was abnormal after cryptorchidism. In 12 of these 15 cases, the echo pattern was very irregular, and two other cases had microlithiasis of the testicular parenchyma, one of them bilaterally. No normal testicular artery was detected in two cases (3%) of normally descended testes, against 18 (20%) amongst those with undescended testes. Epididymal abnormalities were found in two (3%) of the group of normally descended testes against 32 (36%) in the undescended group. CONCLUSIONS: Infertility in patients with cryptorchidism may be a result not only of primary parenchymal degenerative changes of the testis directly due to the condition, but also of operative vascular trauma and epididymal anomalies. Operative trauma may be more common than has generally been believed. Ultrasonography is a suitable method to evaluate post-operatively the prevalence of the testicular abnormalities analysed in the present study.

Adolescent↗

In vivo purging of bone marrow in children with poor-risk neuroblastoma for marrow collection and autologous bone marrow transplantation.

PURPOSE: To evaluate the following prospectively in poor-risk neuroblastoma (NBL) patients: (1) the feasibility and efficacy of in vivo purging of bone marrow; and (2) the outcome after autologous bone marrow transplantation (ABMT) when immunologically tumor-free, unpurged autografts were used. PATIENTS AND METHODS: Twenty-three children with poor-risk NBL were evaluated during induction chemotherapy by repeat bone marrow examinations, including aspirate, biopsy, and an immunofluorescence method using the anti-GD2 monoclonal antibody 3A7. Nineteen patients completed the program with surgery with or without local irradiation followed by ABMT. RESULTS: Autologous bone marrow grafts, both immunologically and cytologically clean, were obtained and used in 19 of 23 children. The overall 4-year disease-free survival of the 19 grafted children was 53%, with a toxic death rate of 16% and a posttransplant relapse rate of 37%. According to the in vivo purging efficacy of the 18 children with initial marrow disease, the following three groups were formed: patients with (1) perfect in vivo purging (n = 5); (2) eventually successful in vivo purging (n = 8); and (3) unsuccesful in vivo purging (n = 5). The 4-year DFS was 100%, 67%, and 0%, respectively (P < 0.001). The five patients with unsuccessful in vivo purging failed because of resistant/progressive bulky disease. CONCLUSION: In patients with poor-risk NBL, in vivo purging of bone marrow by conventional chemotherapy is feasible, can be monitored, and the purging efficacy during the first 3 months after diagnosis is a strong prognostic factor reflecting tumor responsiveness to therapy. Autografting with immunologically clean, unpurged marrows gives a DFS well comparable to previous studies using ex vivo purging.

Adolescent↗

Measurement of testicular volume: comparison of 3 different methods.

PURPOSE: We compared 3 commonly used clinical methods to measure testicular volume. MATERIALS AND METHODS: The volumes of 151 testes in 76 adults treated for cryptorchidism during childhood were measured with an ordinary ruler, an orchidometer and ultrasonography. RESULTS: Mean testicular volume was 15 +/- 8 ml. (standard elevation) measured with a ruler, 16 +/- 7 ml. with an orchidometer and 17 +/- 8 ml. with ultrasonography. The correlation among methods was significant. CONCLUSIONS: To measure testicular size use of an ordinary ruler is recommended for clinical purposes because of its simplicity, availability and low cost.

Adult↗

Early treatment of cryptorchidism, semen quality and testicular endocrinology.

PURPOSE: We evaluated the effect of patient age at treatment of cryptorchidism in relation to subsequent semen quality. MATERIALS AND METHODS: Semen analyses and hormonal evaluations were performed in 51 men who were treated for cryptorchidism at ages 10 months to 12 years. RESULTS: Sperm concentration was normal in 90% of the patients with unilateral and 50% with bilateral cryptorchidism. No patient treated before age 4 years had severe sperm defects. Elevated follicle-stimulating hormone levels indicated severe testicular damage. CONCLUSIONS: Fertility is better in patients with bilateral cryptorchidism if treated before age 4 years. Age at treatment did not have a significant effect on semen quality in patients with unilateral cryptorchidism.

Adolescent↗

Renal transplantation in children with emphasis on young patients.

We report the results of 41 consecutive renal transplantations performed on 39 children (median age 2.7 years). Twenty-six recipients were less than 5 years old. Twenty-one recipients (13 under the age of 5 years) received cadaver (CAD) grafts. All grafts except 2 were from adult donors and were placed extraperitoneally. Patients were on triple immunosuppression (cyclosporine plus azathioprine plus methylprednisolone). Mean follow-up time was 2.3 years. No vascular and only one ureteral complication was seen. Acute tubular necrosis occurred in 3 patients (7.3%). No grafts were lost due to acute rejection. Three-year patient survival and 1-year graft survival were 100%. The overall 3-year actuarial graft survival was 86%. Three-year survival of grafts from living-related donors (LRD) was 92% and that of CAD grafts 75%. In recipients younger than 5 years, 3-year LRD graft survival was '89% and CAD graft survival 73%. No significant differences in graft survival between recipients of different age groups or between LRD and CAD grafts were found. We conclude that results of renal transplantation in children under 5 years of age are comparable to those of older children, even using CAD grafts, when adult donors and triple immunosuppression are used.

Adolescent↗