A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man

Objective　To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. Methods　The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results　Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion　A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation.     

Surgical management of symptomatic spinal metastases. Postoperative outcome and quality of life

STUDY DESIGN: Eighty-six surgical interventions in 76 consecutive patients with symptomatic spinal metastases were reviewed retrospectively. OBJECTIVES: To evaluate the postoperative outcome and quality of life of patients surgically treated for symptomatic spinal metastases. SUMMARY OF BACKGROUND DATA: The standard surgical treatment for patients with symptomatic spinal metastases is anterior spinal cord decompression with stabilization. However, because therapy is only palliative, satisfactory quality of life and high patient acceptance are essential. METHODS: The medical records of all patients were reviewed retrospectively. Furthermore, all surviving patients or the next of kin of deceased patients were interviewed by telephone, and the family doctors or the care-providing physicians of external institutions were contacted. RESULTS: First-choice surgical treatment was anterior spinal cord decompression with stabilization. Postoperative mean survival was 13.1 months, and mean time at home after spinal surgery was 11.1 months. Neurologic improvement with regard to Frankel classification was observed in 58% of the patients, and 93% were able to walk postoperatively. Pain relief was noted in 89%. Overall, 67% of the patients achieved moderate or good general health as shown by the Karnofsky Index, and 80% were satisfied or very satisfied with the surgical intervention. Moreover, 19% of the surgical interventions were associated with complications, local tumor recurrence developed in 22% of the patients, and paraplegia ultimately developed in 18% of patients. CONCLUSIONS: Surgical management of symptomatic spinal metastases, in particular anterior decompression, is of benefit in most metastatic lesions in terms of satisfactory postoperative outcome and quality of life. However, in patients with melanoma or lung carcinoma, the authors advocate spinal surgery only in very exceptional cases.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Serum leptin concentrations in relation to pubertal development

OBJECTIVES: The amount of adipose tissue influences pubertal development and fertility in girls. A candidate for mediating this is the hormone leptin, derived from adipocytes. This work was carried out to determine whether the leptin concentration in serum is regulated during pubertal development. SUBJECTS AND METHODS: Serum concentrations of leptin were determined by radioimmunoassay in a sample of 252 healthy children representing all pubertal stages. RESULTS: Serum leptin concentrations correlated directly with age (r = 0.53), body mass index (BMI) (r = 0.71), and weight for height SD score (r = 0.44) in girls and with BMI (r = 0.33) and weight for height SD score in boys (r = 0.36). Leptin concentrations increased with pubertal development in girls, resulting in significantly higher concentrations at pubertal stages 4 and 5 than at the prepubertal stage, whereas there was no change in the boys. CONCLUSIONS: Serum leptin concentrations increased during pubertal development in the girls, but remained constant in the boys. Whether the increase in serum leptin concentrations in girls is of importance for, or a consequence of, pubertal development is still to be determined.     

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.      

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

Therapy of hematogenous melanoma brain metastases with endostatin.

PURPOSE: Cerebral metastases represent the most common type of brain tumors. This study investigated the effects of endogenous endostatin on hematogenous cerebral melanoma metastases. EXPERIMENTAL DESIGN: Murine K1735 melanoma cells were transfected with the mouse endostatin cDNA. Experimental tumors were induced either by s.c. injection, intracerebral implantation, or via injection into the internal carotid artery to simulate hematogenous metastatic spread. The effects of endostatin expression on tumor incidence, growth pattern, and vascularity were analyzed. RESULTS: In vitro secretion of endostatin by 2.5 x 10(5) cells within 24 hours was 0.12 +/- 0.03 ng, 4.35 +/- 0.4, and 1.18 +/- 0.7 ng/mL for wild type and two endostatin-transfected K1735 clones termed K1735-endo/2 and K1735-endo/8, respectively. Tumor inhibition in vivo correlated with endogenous endostatin production. Within 25 days, growth of s.c. K1735-endo/2 tumors was <20% compared with wild-type controls. Following intracerebral implantation the average survival time of mice was 27.8 +/- 2.6 versus 13.3 +/- 3.7 days in the K1735-endo/2 versus the wild-type group, respectively. Intracarotid injection of 1 x 10(5) wild-type cells killed the mice within 24 +/- 1.8 days. In contrast, endostatin expression prevented macroscopic metastatic tumor growth in 11 of 12 mice, although viable microscopic tumor pockets were detectable in all animals. CONCLUSION: Endostatin inhibits tumor progression of multiple cerebral metastases in vivo. Hematogenous micrometastases are more efficiently suppressed than tumors resulting from high focal cell numbers which may be due to a higher angiogenic signaling exerted by massive cell deposits. Endostatin may prevent solid tumor growth more effectively by inhibition of early angiogenesis.