Validation of computer-assisted manufacture of titanium plates for cranioplasty.

We have constructed 300 titanium cranioplasty plates, over 150 cases using a computerised technique, the remainder by external impression. The clinical follow-up of these cases over 8 years has shown consistently good results that justify our simple low-cost method of manufacturing these plates. Both techniques require the provision of a model on which to construct the plate. In the traditional technique, an approximate model is derived from the resected bone or a direct impression of the defect over the patient's scalp. Using the computerised technique, a more accurate model of the defect and the surrounding bone is milled in polyurethane foam from cross-sectional computerised tomographic (CT) scans. Sheet titanium is pressed to shape from a design outlined on a counterdie. The subsequent stages of the plate construction are then the same for both methods. This study describes the stages of the model manufacture, the validation of its accuracy and the plate construction that follows. Use of the computerised method has resulted in a reduction of errors, enabling the manufacture of a smaller plate than was possible previously. It has also enabled design changes through the achievement of greater accuracy in fit.

The effect of diazepam and promethazine treatment during pregnancy on the somatic development of human offspring.

The postnatal longitudinal somatic, neurological, mental, and behavioral developments were studied in children at birth, 8, 15, and 24 months of life, whose mothers were treated during pregnancy with clinical doses of diazepam (n = 126) and promethazine (n = 127) and whose mothers were unexposed. The latter group was differentiated in negative (n = 256) and positive (n = 102) control children. The positive control group involved mothers who had pregnancy complications similar to those of mothers in the drug groups but who were not treated with CNS-active drugs during pregnancy. It is very difficult to recruit persons for the study and control groups who are appropriate for comparative evaluation. Only firstborns and the so-called "normal" newborn infants were studied; children with low birth weight, major abnormalities, severe neonatal diseases, etc., were excluded. In this article the study design, study materials, and somatic (weight, length, head circumference) development are described. At birth, children had a lower weight in the diazepam group, but it was not noted at the eighth month of postnatal life.

Looking for the causes of the causes.

In the context of research on adverse developmental outcomes it is argued that focusing on the factors correlated with such outcomes-the "causes of the causes"-is likely to suggest more effective approaches to prevention, than focusing on proximate causes of such outcomes. Some reasons are suggested as to why we shy away from the implication that social change will often be needed for effective prevention.

Anesthetic practices in ambulatory aesthetic surgery.

Although ambulatory aesthetic surgery is commonly practiced and information concerning methods of anesthesia is readily available, little is known about the prevalence of various anesthetic practices and whether such practices differ according to the location of surgery. To obtain this information, we sent a carefully structured, 16-page, 69-item questionnaire to the members of the American Society for Aesthetic Plastic Surgery. Six hundred four (76.6 percent) of the 789 actively practicing members returned questionnaires, an exceptionally high response rate. Of interest are the following findings. More than 50 percent of the respondents operate in their offices half or more of the time. About one-half never perform aesthetic surgery in the hospital. Free-standing ambulatory surgical facilities are used less frequently. A wide range of laboratory studies are ordered routinely, regardless of the location of surgery or age of the patient. Local anesthesia with intravenous sedation is widely used in all settings. When employed for office surgery, neither a nurse anesthetist nor an anesthesiologist is present about one-third of the time. General anesthesia is used in half of the office surgical units and is administered by dedicated anesthesia personnel. About half of the time it is administered by an anesthesiologist and about half of the time by a nurse anesthetist. The intensity and methods of patient monitoring are similar in the office, in the hospital, and in a free-standing ambulatory surgical facility. Preoperative laboratory evaluation, monitoring, and the use of anesthetic agents are similar regardless of the surgical setting.

A retrospective study of 66 titanium cranioplasties.

A review was undertaken to assess the outcome of treatment in 66 patients for whom a titanium prosthesis was provided for the repair of a calvarium defect. While many aspects were satisfactory, certain disappointing features led to a prospective pilot study which enabled the following problems to be identified: (a) poor communication between neurosurgeon and prosthetist; (b) difficulties in establishing the margins of the defect; (c) orientation of the prosthesis, and (d) marginal retention. All were overcome with an agreed protocol.

Computer-generated titanium cranioplasty: report of a new technique for repairing skull defects.

A review of 40 cases of titanium cranioplasty fabricated from impressions taken of the defect through the patient's scalp in the conventional way showed that 23% were ill-fitting and 41% of frontal plates had a poor aesthetic result. Attributable factors were difficulty in defining the defect border accurately and limited information of the surrounding tissue architecture which led to strains produced during insertion. Inadequate communication between surgeon and prosthetist compounded these difficulties. A prospective study of six cases fabricated from CT computer-generated models of challenging cranial defects appears to show significant improvements in plate design, resulting in better plate adaptation, stability and aesthetic contour. Plate insertion was rapid (mean time 27 min) thereby minimizing operating time. This paper also discusses the advantages of the enhanced information derived from CT and describes the potential for pre-craniotomy template and matching cranioplasty, thereby permitting a one-stage procedure.

Progeny of male rats treated with methadone: physiological and behavioural effects.

Male rats were injected with methadone HCl (METH) at 5 mg/kg s.c. for 4 days prior to mating with drug-free females. Offspring resulting from these matings were compared with offspring of drug-free males. The progeny of METH-treated males gained less weight after weaning and had lighter thymuses as adults (but not in infancy). Gonadal weights did not differ in infancy or adulthood, and adrenal weights were heavier in female offspring in adulthood. In adulthood METH offspring were significantly different from controls on all behavioural tests used (open field activity, activity cage activity, passive avoidance latencies, shuttle box avoidances, and rotarod latencies), with the differences frequently affected by test order, days of testing, or sex of offspring. The effects in progeny of METH-treated males in the absence of differences in litter size or neonatal mortality indicate that paternal drug ingestion prior to mating can produce physiological and behavioural changes in progeny that are not dependent on detectable effects on early viability or growth.

Long-term effects of naturally occurring within-litter differences in body weight of rats.

From 10 litters of intact Fischer rats, three groups of each sex were formed on the basis of body weight at 30 days of age: Light (L), Medium and Heavy (H). Their weights were examined again at 60, 90, and 120 days. At 60 days the M animals had caught up with the H group, leaving behind the L animals which remained lighter at the end of the experiment. Starting at 63 days, the animals were given several behavioral tests. Behavioral differences between M and H groups existed at the age when weight differences between them had disappeared. The results indicate the longlasting effect of naturally occurring within-litter differences in body weight and behavior. The procedure used may help in studies of longlasting effects of early feeding.

Significance of the biphasic developmental pattern of the hypothalamo-pituitary-adrenocortical system in the rat.

One group of neonatal rats was injected with metopirone at 2-5 days and the second group at 7-10 days of age. At 14 and 21 days all rats treated with metopirone had reduced body and adrenal weights in comparison with their saline-treated littermates. At 21 days the smallest adrenals were in the rats treated with metopirone at 7-10 days. Metopirone increased resting and stress levels of adrenal and plasma corticosterone in the 14-day-old rats and the response to stress by the adrenal corticosterone increase in the 21-day-old rats. The differential effect of metopirone applied in two developmental periods was indicated.

Influence of concurrent testosterone on the effects of methadone on male rats and their progeny.

This study was conducted to test the hypothesis that the adverse effects on progeny that result from administering methadone to male rats are mediated by a decrease in serum testosterone. Male rats were treated with methadone HCl, 10 mg/kg/day for 4 days while an equal number received the same dose plus testosterone propionate, 2.5 mg/kg/day. Neonatal mortality was significantly lower among the progeny of sires which had received the testosterone, 22/132 vs. 33/101, x2 = 8.13, p less than 0.01. The mean body weight at weaning of the progeny of sires treated with methadone plus testosterone was about 4 g lower (p less than 0.01) than that of the progeny of sires which had received methadone only; one-half of this variability was attributable to the greater number of survivors in the former group. Testosterone administered concurrently with methadone to sires resulted in significant reductions in the weights of their testes and adrenals, but increased weights of their seminal vesicles. It was concluded that administration of testosterone concurrent with methadone by preventing dysfunction and/or atrophy of the accessory sex organs of the sire, may have been responsible for the improved neonatal survival of their offspring.

Influence of drug exposure of the father on perinatal outcome.

Initial skepticism that paternally administered drugs could damage the developing fetus has given way to concern that lead, narcotics, ethanol, anticonvulsants, anesthetic gases, caffeine, or cigarette smoke ingested at the time of conception might damage sperm or sperm motility or have indirect effects resulting in an increase in neonatal morbidity and mortality.

Chronic methadone administration to male rats: tolerance to adverse effects on sires and their progeny.

Previous studies have shown that acute administration of methadone to male rats prior to mating results in adverse effects on their progeny, particularly decreased birth weights and increased neonatal mortality. Rather than chronic administration accentuating these effects, results of the present study indicate that tolerance developed so that no adverse effects were found in offspring sired after 21--32 days of methadone administration. In the sire, maintenance of normal weights of accessory sex glands after 4 months of daily methadone suggests that tolerance developed to the CNS effect(s) responsible for the depressed serum LH and testosterone levels found after acute administration of narcotics. In contrast, tolerance did not develop to the inhibition of weight gain produced by methadone administration. No evidence for a dominant lethal effect could be found after chronic methadone administration, in contrast to suggestive evidence for this effect found in previous experiments after acute methadone administration.

Effects of pre- and postnatal litter size reduction on development and behavior of rat offspring.

Litter size was reduced to 2-5 rat pups either prenatally by unilateral maternal oviduct ligation (Group PRN) or postnatally by removing pups (Group PST). Normal size litters (8-10 pups) of sham ligated (SHM) and intact (CON) mothers served as controls. Weights at 30 days were increased by prenatal or postnatal reduction and reduced by prenatal stress (SHM); the sex difference in weight was most pronounced in PRN rats. At 75 days PRN rats were heaviest, with no differences between the other groups. Relative ovarian weights were reduced in PRN females and absolute testes weights increased in PST males. The PRN and SHM females had smaller relative adrenal weights than CON and PST females. Open-field activity was generally increased by prior avoidance conditioning and effects of treatments were found only in groups tested after avoidance-conditioning: PRN and SHM rats were more active than PST and CON rats, particularly on Days 1 (SHM) and 4 (SHM and PRN) of testing. Passive-avoidance behavior of PRN rats was also more susceptible to previous test experience: they emerged more slowly if they had prior open-field experience. The PST animals, in contrast, emerged more rapidly after prior test experience. Plasma corticosterone levels and shuttlebox conditioning and extinction were unaffected by treatments.

Sex difference in the effect of dexamethasone on open-field behavior in rats: gonadal hormones.

PIP: A study was undertaken to determine whether or not the sex differences in the effect of dexamethasone (DEX) on open-field defecation depended on the difference in circulating gonadal hormones in normal male and female rats. The experiment involved ovariectomized females, ovariectomized females given supplementary male hormones, and sham-operated females. In comparison to control groups, all the DEX-treated groups showed a suppression of plasma corticosterone levels, a decrease in weight levels, and reduced adrenal weights. Open-field defecation increased in the DEX-treated female rats but open-field activity was not affected. No differences in behavior or physiological changes were evident between the 3 differently treated groups. These results indicate that sex differences in the response of open-field defecation to DEX-treatment is not the result of sex differences in circulating sex hormones. The response may spring from the organizing effects of the gonadal hormones during the perinatal stage rather than the activating effect of gonadal hormones during adulthood.^ieng