A sweat test centered protocol for the disclosure and diagnosis of cystic fibrosis in a newborn screening program.

We describe the development of a sweat test centered protocol for disclosure and diagnosis of Cystic Fibrosis. Our protocol aims to identify infants early, minimizes the time of uncertainty for the parents, and yet gives them time to begin to come to terms with the possibility of diagnosis. Over a 9-year period 295,247 newborn infants were screened for CF in Wales, of whom 121 infants were diagnosed as having CF. During this period there were four false negatives (3.3%). Parental satisfaction with the process appears very high 6 months after disclosure.

Implications of carrier identification in newborn screening for cystic fibrosis.

OBJECTIVE: To investigate the psychosocial implications for families whose infant was identified as a cystic fibrosis carrier by newborn screening. DESIGN: Prospective psychosocial assessment. SETTING: Primary care. STUDY: (a) families of an affected infant identified by screening (n = 9); (b) families of a carrier infant identified by screening (n = 10). CONTROL: group of mothers from the general population (n = 82). INTERVENTIONS: Questionnaires and semistructured interviews. MAIN OUTCOME MEASURES: Attitude to screening, assessments of the mother/baby relationship, anxiety, wellbeing. RESULTS: All families were in favour of screening, with no evidence that the mother/baby relationship, anxiety or wellbeing had been adversely affected. Parents, however, did identify problems in terms of the service delivery protocol and genetic counselling practice. CONCLUSION: Six months after disclosure, carrier identification was not perceived by parents to be problematic.

Newborn screening for Duchenne muscular dystrophy: a psychosocial study.

OBJECTIVE: To evaluate the psychosocial implications of newborn screening for Duchenne muscular dystrophy. DESIGN: Prospective psychosocial assessment. SETTING: Primary care. STUDY: (a) families of an affected boy identified by screening (n = 20); (b) families of a boy with a transient screening abnormality (n = 18). CONTROL: (a) families of a boy with a later clinical diagnosis (n = 16); (b) random sample of mothers of boys aged 6-9 months (n = 43). INTERVENTIONS: Questionnaires and semistructured interviews. MAIN OUTCOME MEASURES: Attitudes to newborn screening and impact of screening on mother-baby relationship, anxiety/wellbeing, and reproductive patterning within families of an affected boy. RESULTS: Most families of an affected boy were in favour of newborn screening on the grounds of reproductive choice and time to prepare emotionally and practically. There was no evidence of any long term disruption to the mother-baby relationship. Anxiety levels for the screened group were slightly above threshold but returned to normal during the period of the study. There was no evidence, from anxiety or wellbeing scores, that the transient group had suffered any disadvantage. Although the profile of the screened and later clinically diagnosed cohorts was similar after diagnosis, when boys from the screened cohort were 4 years old and more socially aware, their profile was more positive. There was evidence that reproductive patterning had been modified, and four fetuses carrying a mutation causing Duchenne muscular dystrophy were terminated. CONCLUSION: A case can be made for newborn screening provided that the test is optional, a rigorous protocol for service delivery is used, and an infrastructure providing continuing support is in place.

Effects of a bioactive glass on healing of closed skin wounds in dogs.

OBJECTIVE: To determine effects of intraincisional bioactive glass on healing of sutured skin wounds in dogs. ANIMALS: 9 purpose-bred mature female Beagles. PROCEDURE: 3 small matched bilateral (treated vs control) full-thickness truncal skin incisions were made and sutured. Treated wounds received intraincisional particulate bioactive glass prior to closure. Laser Doppler perfusion imaging was used to assess percentage change in tissue perfusion 3 and 5 days after incision on 1 set of 2 matched wounds, and skin and subcutaneous tissue-cutaneous trunci breaking strength were assessed at 5 days. The other 2 sets of wounds were used for histologic evaluation at 5 and 21 days, respectively. RESULTS: Subjective signs of gross inflammatory reaction were not detected in treated or control wounds. At 5 days, median subcutaneous tissue-cutaneous trunci breaking strength was significantly higher in treated wounds than in control wounds-(188.75 vs 75.00 g). At 5 days, median scores were significantly higher for neutrophils (1 vs 0), macrophages (2 vs 1), and necrosis (1 vs 0) for treated wounds than for control wounds. At 21 days, median macrophage scores were significantly higher for treated wounds than for control wounds (2 vs 1). CONCLUSIONS AND CLINICAL RELEVANCE: Bioactive glass in soft tissues does not cause a gross inflammatory reaction but causes an increase in histologic signs of inflammation, which decreases with time. Bioactive glass has potential for increasing tissue strength. Increased subcutaneous breaking strength could be beneficial in treating wounds in which early healing strength is needed.

MR imaging of cyclops lesions.

OBJECTIVE: Localized anterior fibrosis (cyclops lesion) is a known cause of extension loss of the knee after anterior cruciate ligament (ACL) reconstruction. We describe MR imaging as a noninvasive diagnostic tool to examine cyclops lesions. SUBJECTS AND METHODS: Thirty-three MR studies of 31 patients with residual persistent extension loss after ACL reconstruction using patellar tendon autograft were reviewed and compared with results of second arthroscopy. We used MR imaging to describe the ACL graft signal intensity and course, tibial and femoral tunnel placement. quantitative measurements of notch size and shape, and the presence or absence of cyclops lesions. When a cyclops lesion was revealed on MR imaging, the signal-intensity characteristics, location, and size were documented. Preoperative MR imaging findings were then correlated with findings at arthroscopy. RESULTS: The sensitivity, specificity, and accuracy of revealing a cyclops lesion on MR imaging were 85.0%, 84.6%, and 84.8%, respectively. We found no statistically significant differences in the size of intercondylar notches for patients with and patients without cyclops lesions. CONCLUSION: MR imaging was sensitive, specific, and accurate in revealing cyclops lesions in a subgroup of patients with extension loss after ACL reconstruction.

Neurotrophic factors BDNF and GDNF protect embryonic chick spinal cord motoneurons from ethanol neurotoxicity in vivo.

Maternal consumption of ethanol is widely recognized as a leading cause of mental and physical deficits. Many populations of the central nervous system are affected by the teratogenic effects of ethanol. Neurotrophic factors (NTFs) have been shown to protect against ethanol neurotoxicity in culture, although there have been no demonstrations of such protection in vivo, in specific neuronal populations. Previous studies have demonstrated that ethanol is toxic to developing chick embryo motoneurons when administered from embryonic day 10 (E10) to E15. NTFs such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) have been shown to support developing spinal cord motoneurons, and when exogenously applied, decrease naturally occurring cell death, and protect against axotomy. The concurrent delivery of BDNF or GDNF with ethanol to the embryonic chick from E10 to E15 was designed to examine the capacity of these NTFs to provide in vivo neuroprotection for this ethanol-sensitive motoneuron population. Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels. This study represents the first demonstration of in vivo neuroprotection from ethanol toxicity with respect to specific neuronal populations.

Bursoscopy of the trochanteric bursa.

We report two cases in a single patient with severe, refractory trochanteric bursitis, treated successfully with bursoscopy and bursectomy. The symptoms, clinical findings, surgical technique, and short-term results are described.

Construction of a weight-bearing surface on a dog's distal pelvic limb.

A one-year-old, neutered female boxer presented with a self-inflicted pandigital amputation following complications of a left hind footpad laceration repair. A meshed skin graft was placed distally over the exposed granulation tissue of the affected limb. In two surgical procedures, a total of five 6 by 8-mm and three 8 by 10-mm digital pad grafts were transplanted into recessed sites in the granulation tissue over the distal aspect of the metatarsal bones. A newly designed pressure relief bandage/ splint was used to assist maturation of the grafts. The result was a weight-bearing surface over an area of maximum tissue stress.

Congenital hypothyroidism in Wales (1982-1993): demographic features, clinical presentation and effects on early neurodevelopment.

OBJECTIVE: Neonatal screening for congenital hypothyroidism (CH) was introduced in Wales in 1982. The aim of the study was to evaluate the demographic features and characteristics of infants identified during the first 12 years of screening and their neurodevelopmental progress in the first 2 years of life. DESIGN: Prospective collection of biochemical and clinical data (including results of Griffiths Mental Development Scales) obtained from questionnaires sent to paediatricians responsible for the ongoing clinical care of children with CH. PATIENTS: In Wales, between 1982 and 1993, 136 infants with primary congenital hypothyroidism (CH) were identified by the neonatal screening programme. RESULTS: Of all new-borns, 99.8% were screened and the prevalence of CH was 1 in 3279 (1 in 2473 girls and 1 in 4770 boys). The prevalence of CH was increased in North Wales. CH was associated with increased birth weight (48.5% of infants weighed greater than 3.5 kg) and an increased prevalence of non-thyroidal congenital abnormalities (8%) and congenital heart disease (3%). Isotope scanning demonstrated an increased prevalence of normal or enlarged thyroid glands and fewer ectopic glands compared to those reported in other studies. The mean developmental quotients (DQs) for individual subsets of intellectual and behavioural functioning in children with CH aged 1 and 2 years were all above 100 (range: 103.5-111.9). In subjects with absent thyroids, these DQs were correlated with the serum concentrations of free thyroxine before treatment. CONCLUSIONS: The demographic features of infants with congenital hypothyroidism born in Wales are similar to those reported from other European studies although there are marked regional variations in prevalence within Wales for which there is no apparent explanation. The median age of starting therapy was 17 days and compares favourably with other screening programmes. The overall mental development of Welsh children aged 1 and 2 years with congenital hypothyroidism identified by neonatal screening is satisfactory.

Tryptophan metabolism in alcoholism. Tryptophan but not excitatory amino acid availability to the brain is increased before the appearance of the alcohol-withdrawal syndrome in men.

Tryptophan (Trp) metabolism and disposition and excitatory and other amino acid concentrations were determined in alcohol-dependent subjects in relation to the alcohol-withdrawal syndrome (AWS). Parameters were examined in 12 alcohol-dependent male subjects, undergoing elective upper digestive tract tumour resection, and 12 age-, gender-, and medication-matched controls on three occasions: pre-operatively, post-operatively, and immediately before (i.e. within 24 h of) the appearance of the AWS. No significant differences were observed between controls and alcoholic subjects on the first or second of these occasions. On the third occasion, within 24 h of the appearance of the AWS, alcoholics showed a dramatic elevation (117%) in free serum Trp concentration and a consequent increase (111%) in the ratio of [free Trp]/[competing amino acids], which is an accurate predictor of Trp entry into the brain. Increases were also observed on this third occasion in concentrations of total Trp (49%), cortisol (123%), and norharman (137%). Concentrations of glutamate, glycine, aspartate, serine, and taurine did not differ significantly within or between the control and alcohol-dependent groups of subjects on any of the three occasions. The possible significance of the Trp and related metabolic changes in relation to the behavioural features of the AWS is discussed.

No early effects of electroconvulsive therapy on tryptophan metabolism and disposition in endogenous depression.

The possibility that a single electroconvulsive therapy (ECT) could increase tryptophan (Trp) availability to the brain for 5-hydroxytryptamine (5-HT, serotonin) synthesis was examined in 10 depressed patients before and during the 1st hour following an ECT and in 4 control (minor ear, nose, and throat surgical) subjects receiving similar premedication. Trp availability to the brain, expressed as the serum Trp: competing amino acid ratio, and related aspects of Trp disposition were not significantly altered by ECT any differently than from preoperative stress and premedication. We suggest that Trp availability to the brain and, hence, cerebral 5-HT synthesis are not altered in depressed patients early after a single ECT.

Serum biochemical values in sled dogs before and after competing in long-distance races.

OBJECTIVE: To measure and compare blood values in sled dogs before and after long-distance racing. DESIGN: Prospective study. ANIMALS: 17 adult sled dogs in the 1991 Iditarod Trail Sled Dog Race and 21 in a simulated sled dog race. PROCEDURE: Blood samples were obtained from 17 dogs 7 days before they began and after they finished (finisher group) or were eliminated from (nonfinisher group) the Iditarod Trail Sled Dog Race. Blood samples were also obtained from 21 dogs before and after a simulated sled dog race. RESULTS: In finisher-group dogs, BUN and uric acid (UA) concentrations were increased after racing; nonfinisher-group dogs had significantly lower postrace BUN and UA concentrations. Significant increases in creatine kinase (CK) and aspartate transferase (AST) activities were detected in all dogs after racing, and postrace values were higher in nonfinisher-group dogs, compared with finisher-group dogs. Mean alkaline phosphate activities were significantly increased after racing in nonfinisher-group dogs only. In dogs that ran the simulated race, postrace values for serum albumin, total protein, calcium, and potassium concentrations, as well as Hct, hemoglobin concentration, and RBC count, were significantly lower than prerace values. Postrace values for alkaline phosphate, alanine transaminase, AST, lactate dehydrogenase, CK, BUN, and UA were significantly higher than prerace values. CLINICAL IMPLICATIONS: High CK activities are indicative of severe muscle degeneration and, in sled dogs, may represent a degree of muscle breakdown beyond which a dog cannot continue to work. Markedly high CK, and possibly AST, serum activities may be indicators of performance failure in sled dogs competing in long-distance races.

Ethanol influences on the chick embryo spinal cord motor system. II. Effects of neuromuscular blockade and period of exposure.

The study described below was performed as a continuation of a previous study in which we found reduced motoneuron number in lumbar spinal cord of the chick embryo following chronic ethanol administration from embryonic day 4 (E4) to E11. We sought to determine whether this reduction was due to primary ethanol toxicity or to enhancement of naturally occurring cell death (NOCD) and to determine whether administration of ethanol at a later period of development could also reduce motoneuron number. Earlier studies have shown that curare suspends NOCD in the chick embryo. By administering both ethanol and curare to these embryos from E4 to E11 and examining the lumbar spinal cord on E12, we determined that ethanol was directly toxic to motoneurons and reduced motoneuron number in the absence of NOCD. By administering ethanol from E10 to E15 and examining the lumbar spinal cord on E16, we determined that ethanol can reduce motoneuron number without altering spinal cord length during more than one stage of chick embryo development, and that ethanol toxicity is not dependent on NOCD. In addition, we demonstrated that ethanol does not affect the neurotrophic content of chick muscle when it is administered from E10 to E15.

Long-term trends and sources of organochlorine contamination in Canadian tundra Peregrine Falcons, Falco peregrinus tundrius.

Levels of eggshell thinning, and organochlorine residues in egg contents, blood plasma of adults and juveniles, tissue samples, and prey species were determined for a population of migratory Peregrine Falcons (Falco peregrinus tundrius) breeding in the Canadian Arctic. Temporal trends were assessed by comparing data collected during 1991-1994, with data from 1982-1986, for the same population. Shells (n=54) from 1991-1994 averaged 15% thinner than eggs produced prior to the introduction of DDT. No improvement in shell thickness was detected between decades. Mean DDE residue levels in eggs showed a decline from 7.6 mg kg (1982-1986) to 4.5 mg kg (1991-1994), but there was no significant change in SigmaPCB residues. Moreover, the proportion of clutches with eggs exceeding critical SigmaPCB, DDE, and dieldrin residue levels (10%) did not change between decades. Relative to Greenland and Alaskan populations, F. p. tundrius at Rankin Inlet show high levels of organochlorine contamination and little reduction in residues over the last decade. These Tundra Peregrines continue to be exposed to organochlorines in Latin America; however, results also link relatively high levels in the study population with waterfowl species that do not leave Canada in winter.

Evaluation of closed-suction drainage for treating auricular hematomas.

The principal and dynamics of closed-suction wound drainage lend themselves to use on auricular hematomas. This type of drainage was evaluated in the treatment of 10 auricular hematomas on nine animals. Seven animal owners rated the results of the procedure as "good," and two rated them as "fair." The two rating the procedure as having "fair" results owned dogs with allergic dermatitis, and the auricular hematomas recurred. In both dogs, auricular hematomas again recurred after other means of treatment were used. If the pocket for the vacuum tube is not secure and the animal is quite active, or if it molests the bandage, or both, it is possible for the tube to break or the needle to come off of the tubing.

In vitro comparison of the effects of ethanol and acetaldehyde on dorsal root ganglion neurons.

Results of previous experiments designed to investigate the role of acetaldehyde, the primary metabolite of ethanol, have been contradictory. Experiments have provided evidence that supports and refutes the idea that acetaldehyde is responsible for the teratogenic effects observed in fetal alcohol syndrome. In the present study, cell culture techniques were used to examine the effects of acetaldehyde, both independently and in conjunction with ethanol. The purpose was to determine whether acetaldehyde had any effect on survival and process outgrowth of dorsal root ganglion (DRG) neurons cultured in vitro. This study revealed that acetaldehyde was as toxic to DRG survival as is ethanol, but had a lesser effect on neurite outgrowth than ethanol. Also, acetaldehyde and ethanol do not act synergistically to damage neurons in culture. The results indicate that, although acetaldehyde is probably not solely responsible for ethanol neurotoxicity, it does exhibit a secondary toxicity that could be the subject of future studies.

Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression.

Acute ethanol consumption by fasting male volunteers decreases circulating trytophan (Trp) concentration and availability to the brain as determined by the ratio of (Trp) to the sum of its five competitors ([Trp]/[CAA]ratio). These effects of alcohol are specific to Trp, because levels of the 5 competitors are not increased. The decrease in circulating (Trp) is not associated with altered binding to albumin and may therefore be due to enhancement of hepatic Trp pyrrolase activity. It is suggested that, under these conditions brain serotonin synthesis is likely to be impaired and that, as a consequence, a possible strong depletion of brain serotonin in susceptible individuals may induce aggressive behaviour after alcohol consumption. The possible implications of these findings in the relationship between alcohol and depression are also briefly discussed.

Ethanol influences on the chick embryo spinal cord motor system: analyses of motoneuron cell death, motility, and target trophic factor activity and in vitro analyses of neurotoxicity and trophic factor neuroprotection.

A series of in vivo and in vitro experiments were conducted to determine the influence of prenatally administered ethanol on several aspects of the developing chick embryo spinal cord motor system. Specifically, we examined: (1) the effect of chronic ethanol administration during the natural cell death period on spinal cord motoneuron numbers; (2) the influence of ethanol on ongoing embryonic motility; (3) the effect of ethanol exposure on neurotrophic activity in motoneuron target tissue (limb bud); and (4) the responsiveness of cultured spinal cord neurons to ethanol, and the potential of target-derived neurotrophic factors to ameliorate ethanol neurotoxicity. These studies revealed the following: Chronic prenatal ethanol exposure reduces the number of motoneurons present in the lateral motor column after the cell death period [embryonic day 12 (E12)]. Ethanol tends to inhibit embryonic motility, particularly during the later stages viewed (E9-E11). Chronic ethanol exposure reduces the neurotrophic activity contained in target muscle tissue. Such diminished support could contribute to the observed motoneuron loss. Direct exposure of spinal cord neurons to ethanol decreases neuronal survival and process outgrowth in a dose-dependent manner, but the addition of target muscle extract to ethanol-containing cultures can ameliorate this ethanol neurotoxicity. These studies demonstrate ethanol toxicity in a population not previously viewed in this regard and suggest a mechanism that may be related to this cell loss (i.e., decreased neurotrophic support).