Very low birth weight children at school age: comparison of neonatal management methods

The outcome of 293 infants born to a geographically defined community and weighing 501-1500 g was investigated. Medical intervention in the newborn period had been avoided. Morbidity was assessed at school age. Of the infants, 236 had been live born in the labour ward of this hospital; of these, 117 (49.6%) died in the neonatal period, one (0.4%) died in the first year, four (1.7%) were untraced, 13 (5.5%) had major handicap, 29 (12.3%) had minor handicap, and 72 (30.5%) were considered to be normal. In terms of survival, handicap, and intellectual with that of infants born over the same period (1963-71) in areas where intensive methods of perinatal care were used. These results imply that postnatal survival and potential of infants of very low birth weight are by no means prejudiced when only experienced nursing care is available.     

Evaluation of the developmental toxicity of methacrylonitrile in Sprague-Dawley rats and New Zealand white rabbits

Timed-pregnant Sprague-Dawley (CD) outbred rats and New Zealand White rabbits were dosed by gavage with methacrylonitrile (MACR) in distilled water during major organogenesis. Rats were dosed on Gestational Days (GD) 6 through 15 (0, 5, 25, or 50 mg MACR/kg/day) and rabbits on GD 6 through 19 (0, 1, 3, or 5 mg MACR/kg/day). Maternal clinical status was monitored daily during treatment. At termination (GD 20, rats; GD 30, rabbits), confirmed-pregnant females (25-26 per group, rats; 17-22 per group, rabbits) were evaluated for clinical status and gestational outcome; each live fetus was examined for external, visceral, and skeletal malformations. In rats, no treatment-related maternal clinical signs or mortality were observed, nor was there any adverse effect on maternal body weight or food or water consumption. At necropsy, absolute, relative, and adjusted maternal liver weight was increased at the mid- and high-dose groups, an effect that may be indicative of induction of hepatic enzymes rather than toxicity. In the absence of any indication of maternal toxicity, the no-observed-adverse-effect level (NOAEL) for maternal toxicity in this study was >/=50 mg MACR/kg/day. The NOAEL for developmental toxicity in rats was also >/=50 mg MACR/kg/day. There was no effect of treatment on postimplantation loss, mean fetal body weight per litter, or morphological development. In rabbits, maternal mortality and clinical signs were not dose related. Maternal food consumption, body weight, and liver weight were not adversely affected by treatment. Thus, the maternal NOAEL was >/=5 mg MACR/kg/day. Maternal toxicity, including death, was observed >/=7.5 mg/kg/day in preliminary studies. The developmental NOAEL was also >/=5 mg MACR/kg/day. There was no adverse effect of treatment on postimplantation loss or fetal body weight. A significant decrease in the percentage male fetuses per litter was observed, although there was no effect on total live litter size, suggesting that the reduction in the ratio of live male fetuses in the high-dose group was not biologically significant. MACR had no adverse effect on morphological development. In summary, oral administration of MACR to rats and rabbits during organogenesis, at doses that did not cause persistent maternal toxicity (50 mg MACR/kg/day, rats; 5 mg MACR/kg/day, rabbits), also did not cause any adverse developmental effects.     

Nerve growth factor (NGF)-mediated protection of neural crest cells from antimitotic agent-induced apoptosis: the role of the low-affinity NGF receptor

Prevention by nerve growth factor (NGF) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low-affinity (p75) or high-affinity (trkA) receptor or to a cooperative interaction between the two. In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal antibody that binds to the NGF-binding domain of p75, we demonstrate that NGF binding to p75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents.     

Detection of human papillomavirus in routinely processed biopsy specimens from laryngeal papillomas: evaluation of reproducibility of polymerase chain reaction and DNA in situ hybridization procedures

The frequency of human papillomavirus (HPV) in laryngeal papillomas varies largely among different studies. DNA in situ hybridization (ISH) has been the most widely used method for detection of HPV. The aim of this study was to compare the reproducibility and sensitivity of ISH with polymerase chain reaction (PCR) in 35 specimens of laryngeal papillomas routinely fixed in buffered or unbuffered formalin. Out of 12 specimens fixed in buffered formalin, 10 were positive for HPV 6/11 using ISH. The procedure was repeated three times and three specimens were positive only twice. Nine biopsies were positive for HPV using PCR with consensus primers (My 09/11) on dewaxed tissue without extracting DNA. In three repeated PCRs, the results were inconsistent in three samples. After DNA extraction, all 12 samples were positive with PCR. Of the 23 specimens fixed in unbuffered formalin, 14 were HPV-positive with ISH, while only one was positive with PCR. We concluded that PCR with My 09/11 consensus primers is a highly sensitive method for detection of HPV in laryngeal papillomas fixed in buffered formalin, but useless for samples fixed in unbuffered formalin. When DNA was extracted from the former type of fixed tissue, the results were highly reproducible. In contrast to PCR, ISH appeared to be less influenced by fixation procedure, but it was not as reproducible and sensitive as PCR. Negative results did not necessarily mean absence of HPV.     

Growth hormone deficiency in adults]

Growth hormone (GH) has been in clinical use for almost 40 years to promote linear growth in growth hormone deficient children. Treatment has usually been stopped after the epiphyseal plates have fused or when the person reaches a proper height. Previously, GH replacement therapy in adults was not deemed clinically indicated. GH-deficiency in adults is now accepted as a clinical entity, manifested by cardiovascular dysfunction, dyslipidemia, reduced capacity for exercise and muscular weakness, altered body composition, increased prevalence of osteoporosis, and impaired psychological well-being. The treatment of adults used to be unrealistic, because of the limited supply of human pituitary-derived GH. Moreover, the risk of transferring Creutzfeldt-Jakobs disease led to a stop in the therapeutic use of pituitary GH preparations. The availability of recombinant human prion-free GH has made replacement therapy possible in GH-deficient adults. In this review, the GH deficiency syndrome in adults is described, together with the results of recent clinical studies of GH replacement treatment in adults.     

The Charing Cross Hospital experience with temozolomide in patients with gliomas

Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4-week intervals. There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 (30%) fulfilled the criteria for an objective response. There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 (25%) fulfilled the criteria for an objective response. This gave an overall objective response rate of 20 (27%) out of 75 patients. Temozolomide was generally well tolerated, with little subjective toxicity and predictable myelosuppression. However, the responses induced with this schedule were of short duration and had relatively little impact on overall survival. In conclusion, temozolomide given in this schedule has activity against high grade glioma. However, studies evaluating chemotherapy in primary brain tumours should include a quality-of-life/performance status evaluation in addition to CT or MRI scanning assessment.     

Morphometric video analysis of the engine-driven nickel-titanium Lightspeed instrument system

Two hundred and sixteen Lightspeed instruments were evaluated microscopically for the presence of corrosion, surface debris, and alloy defects. The instruments were assessed morphometrically for consistency of physical design and dimensions by measuring and analyzing eight parameters of the instrument pilot tips, heads, and shafts. Results from visual inspection showed that none of the instruments were corroded; 23 presented surface porosities, and 17 had sharp strips of alloy. Data obtained by morphometric analysis indicated the mean diameter of the head of only 7 of 18 sizes met the +/- 0.02 mm allowable tolerance set forth by the American Dental Association (ADA) Specification No. 28. Observation and video analysis indicated that instruments of the same size adhere to the same basic design, but that morphometric variations do exist. The visual and intersize analysis indicated that the Lightspeed is not an instrument of any one determined shape that changes only in diameter. Rather, it is a series of instruments that show gradual shifts in both size and shape as the instrument size increases. Lightspeed instruments are a new type of nickel-titanium endodontic instrument that cannot be evaluated using the standards proposed by the American National Standards Institute/ADA Specification No. 28 for files and reamers.     

Small bowel injury in gastroschisis: relation to fetal presentation

The study presented here attempts to assess the cost savings attributable to having an on-site corporate medical clinic. For a period of 4 months, employees using the clinic were surveyed regarding: (1) whether they would have used an outside doctor if the corporate medical department clinic were not available, and (2) how many days per year they estimated that they came to work because there was an on-site medical center when they would otherwise have stayed at home. The results indicated that, on average, employees who used the facility saved 3.3 days of absenteeism. That total cost savings was calculated to be $499,212 per year. In addition, 69% of employees indicated that they would have sought attention elsewhere, suggesting that the presence of an on-site medical center does not induce demand. The findings concerning the hidden savings brought about by an on-site medical center are also discussed.