Malignancies in UK children with HIV infection acquired from mother to child transmission

By April 1995, 302 cases of vertically acquired HIV infection had been reported through the British Paediatric Association Surveillance Unit. Over 50% of these children had developed an AIDS indicator disease, including nine malignancies (seven cases of non-Hodgkin's lymphoma (NHL) and two of Kaposi's sarcoma). There were two other malignancies that were not AIDS indicator diseases. In children less than 5 years of age the incidence of NHL was approximately 2500 times greater than expected in the UK child population. Three children presented with NHL as their AIDS indicator disease and four developed NHL at a median of 14 (range 10-19) months after the initial diagnosis of AIDS. Six of the seven children died at a median of 6.5 (range 2-14) months after the diagnosis of NHL. The seventh child responded to treatment and is alive nearly four years later. Histology was available in five cases, of which four were of B cell and one of T cell origin. Epstein-Barr virus was detected in all three patients with NHL where it was sought; all had B cell lymphomas. Although comparatively rare, malignancies occur in children infected with HIV and may be the presenting illness. Paediatricians now need to consider HIV infection as a predisposing cause of childhood cancer, especially NHL.     

Incidence of insulin dependent diabetes mellitus in Karachi, Pakistan

OBJECTIVES: To determine the incidence of insulin dependent diabetes mellitus (IDDM) among children aged up to 16 years residing in the city of Karachi, Pakistan, during the five years from 1989 to 1993. DESIGN: Retrospective study of incidence using hospital and clinic records. SETTING: The city of Karachi, Pakistan. SUBJECTS: Children satisfying standard criteria for the diagnosis of IDDM, attending treatment facilities for the first time during the study period. MAIN OUTCOME MEASURES: The incidence of IDDM in this population and its variation by age and sex. RESULTS: The incidence of IDDM in this population is 1.02/100000 per year, which is one of the lowest incidence rates yet reported. CONCLUSIONS: The very low incidence of IDDM, contrasted with the substantially higher incidence among migrants, supports the view that environmental factors are the major determinants of variations in the incidence of this condition between populations.     

Improvement in Obesity-associated Medical Conditions following Vertical Banded Gastroplasty and Gastrointestinal Bypass

Thirty-nine patients undergoing either Silastictrade mark ring vertical banded gastroplasty (SRVG, n = 23) or Roux-en-Y gastrointestinal bypass (RGB, n = 16) over a 1-year period were analyzed retrospectively. Weight loss averaged 40 kg (89 lb). Clinical diabetes mellitus was markedly improved in seven out of nine patients (p = 0.023). Shortness of breath resolved in all 26 patients who had this condition preoperatively (p < 0.001). Orthopedic problems, high blood pressure, and self-assessment of general health and quality of life were also dramatically improved. We conclude that bariatric surgery serves as an effective method to alleviate a multitude of conditions associated with morbid obesity.     

Improvement in appropriate autologous donations with local education: 1987 to 1989

Preoperative autologous blood donation for elective surgery patients at university hospitals was underused in the past. More recently, national educational efforts have been made. To test the impact of local surgeon interviews and education, in 1988 the same local educational program was instituted at three university hospitals; three community hospitals were used as controls. Donation by appropriate patients of interviewed surgeons (elective surgery, crossmatch recommended, no contraindications to donation) increased from 24 percent (44/180) to 40 percent (88/222) (p = 0.002) and 15 percent (21/143) to 32 percent (41/127) (p = 0.001) at two university hospitals where the investigator-educators were on site, but not at the three community hospitals. Between 1987 and 1989, donation rates at all six hospitals remained low among patients for whom autologous donation was (probably) less appropriate. Donation rates for type and screen procedures were 3.0 percent (131/4587) in 1987 and 3.0 percent (199/6606) in 1989 (p = 0.67). Donation rates for "no blood order" procedures were 0.2 percent (15/9429) in 1987 and 0.1 percent (9/11,239) in 1989 (p = 0.14). It can be concluded that appropriate autologous blood donations increased at university hospitals where surgeons were individually interviewed and educated by an investigator on site. However, despite this increase, apparently eligible elective surgery patients in 1989 still failed to donate. This situation deserves additional investigation.     

Balance of cell proliferation and apoptosis in breast carcinogenesis

We determined the mitotic and apoptotic index through the spectrum of preinvasive ductal breast lesions to invasive carcinoma in search of disturbances in the proliferation/cell death balance in breast carcinogenesis. Seventytwo pure preinvasive ductal breast lesions (without invasive carcinoma) and 103 invasive breast carcinomas were used. The numbers of mitotic and apoptotic cells were microscopically counted in hematoxylin and eosin stained sections (MI and Al, respectively), and the ratio of the values of MI and AI was calculated for each individual case (M/A index).A distinction was made between well differentiated and poorly differentiated breast lesions, based on histological type and nuclear grade, to arrive at two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 6fold from DCIS to well differentiated invasive carcinoma. The AI remained in the same range, resulting in a 4fold increase of the M/A index. For the poorly differentiated breast lesions, a significant increase in MI and AI was found from hyperplasia to poorly differentiated DCIS. From DCIS to poorly differentiated invasive carcinoma, the MI increased significantly and the AI decreased 2fold (n.s.), resulting in a 2.5fold significant increase of the M/A index.In conclusion, the net increase of the number of cells in the transition from well differentiated preinvasive to well differentiated invasive carcinoma is accompanied by an increase of cell proliferation rather than decrease in apoptosis, suggesting that in these lesions, proliferation related mechanisms are most important in carcinogenesis and progression. In contrast, in poorly differentiated breast lesions, decreased apoptosis seems to be also important in carcinogenesis and progression. At present, we are gathering patients with invasive breast cancer who had a previous biopsy with a preinvasive lesion to obtain further more direct evidence for this hypothesis.     

Physical and mental development in 4-6-year-old triplets

A total of 21 families with complete sets of triplets, born within 200 km of Stockholm, were invited to participate in a follow-up study with the aim of assessing the physical and mental development of their triplets at 4-6 years of age. Four families declined to participate in the study and thus the study group consisted of 17 sets of triplets who were born at 33-36 gestational weeks from 1986 to 1989. Mean birth weight was 2104g (range 1310-2670g) for the boys and 1882g (range 1290-2590g) for the girls. At birth, none of the 51 triplets showed any malformations. No asphyxia or other major complications were noted to have occurred at delivery. The children were examined in their homes with a neurological examination and the Griffiths mental development scales (GMDS). No major physical disabilities were found. In a group of triplets born small for dates, the total GMDS score and most of the subscale scores were significantly lower than for their siblings. In contrast to what has been found in singletons and twins, the differences in mental development between triplet boys and girls were not significant. On the whole, physical and mental development did not differ from what has been found in twins and singletons of the same age and with the same birth weight.     

Plasma cytokine levels in necrotizing enterocolitis

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.     

Necrotizing enterocolitis—multisystem organ failure of the newborn?

Evidence of failure of organ system other than the gastrointestinal tract was reviewed in a series of 46 infants treated for necrotizing enterocolitis (NEC) at a regional combined medical and surgical neonatal unit. Respiratory failure was identified in 42 infants (91%), renal failure in 39 (85%), cardiovascular failure in 15 (33%) and hepatic failure in 7 (15%). The number of systems involved correlated with both severity of disease and outcome. Onset of failure in the above systems was closely related to the diagnosis of NEC and 29 cases predated the clinical onset. We conclude that NEC is part of a syndrome of multisystem failure and that this has important implications for the treatment of NEC.