Nrl is required for rod photoreceptor development.

The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors. It acts synergistically with Crx to regulate rhodopsin transcription. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.

Retinopathy induced in mice by targeted disruption of the rhodopsin gene.

Retinitis pigmentosa (RP) represents the most common mendelian degenerative retinopathy of man, involving death of rod photoreceptors, cone cell degeneration, retinal vessel attenuation and pigmentary deposits. The patient experiences night blindness, usually followed by progressive loss of visual field. Genetic linkage between an autosomal dominant RP locus and rhodopsin, the photoreactive pigment of the rod cells, led to the identification of mutations within the rhodopsin gene in both dominant and recessive forms of RP. To better understand the functional and structural role of rhodopsin in the normal retina and in the pathogenesis of retinal disease, we generated mice carrying a targeted disruption of the rhodopsin gene. Rho-/- mice do not elaborate rod outer segments, losing their photoreceptors over 3 months. There is no rod ERG response in 8-week-old animals. Rho+/- animals retain the majority of their photoreceptors although the inner and outer segments of these cells display some structural disorganization, the outer segments becoming shorter in older mice. These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potential of re-introducing functional rhodopsin genes into degenerating retinal tissues.

Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse.

X-linked juvenile retinoschisis (XLRS) is a neurodevelopmental abnormality caused by retinoschisin gene mutations. XLRS is characterized by splitting through the retinal layers and impaired synaptic transmission of visual signals resulting in impaired acuity and a propensity to retinal detachment. Several groups have treated murine retinoschisis models successfully using adeno-associated virus (AAV) vectors. Owing to the fragile nature of XLRS retina, translating this therapy to the clinic may require an alternative to invasive subretinal vector administration. Here we show that all layers of the retinoschisin knockout (Rs1-KO) mouse retina can be transduced efficiently with AAV vectors administered by simple vitreous injection. Retinoschisin expression was restricted to the neuroretina using a new vector that uses a 3.5-kb human retinoschisin promoter and an AAV type 8 capsid. Intravitreal administration to Rs1-KO mice resulted in robust retinoschisin expression with a retinal distribution similar to that observed in wild-type retina, including the expression by the photoreceptors lying deep in the retina. No off-target expression was observed. Rs1-KO mice treated with this vector showed a decrease in the schisis cavities and had improved retinal signaling evaluated by recording the electroretinogram 11-15 weeks after the application.

Constitutive "light" adaptation in rods from G90D rhodopsin: a mechanism for human congenital nightblindness without rod cell loss.

A dominant form of human congenital nightblindness is caused by a gly90-->asp (G90D) mutation in rhodopsin. G90D has been shown to activate the phototransduction cascade in the absence of light in vitro. Such constitutive activity of G90D rhodopsin in vivo would desensitize rod photoreceptors and lead to nightblindness. In contrast, other rhodopsin mutations typically give rise to nightblindness by causing rod cell death. Thus, the proposed desensitization without rod degeneration would be a novel mechanism for this disorder. To explore this possibility, we induced mice to express G90D opsin in their rods and then examined rod function and morphology, after first crossing the transgenic animals with rhodopsin knock-out mice to obtain appropriate levels of opsin expression. The G90D mouse opsin bound the chromophore and formed a bleachable visual pigment with lambda(max) of 492 nm that supported rod photoresponses. (G+/-, R+/-) retinas, heterozygous for both G90D and wild-type (WT) rhodopsin, possessed normal numbers of photoreceptors and had a normal rhodopsin complement but exhibited considerable loss of rod sensitivity as measured electroretinographically. The rod photoresponses were desensitized, and the response time to peak was faster than in (R+/-) animals. An equivalent desensitization resulted by exposing WT retinas to a background light producing 82 photoisomerizations rod(-1) sec(-1), suggesting that G90D rods in darkness act as if they are partially "light-adapted." Adding a second G90D allele gave (G+/+, R+/-) animals that exhibited a further increase of equivalent background light level but had no rod cell loss by 24 weeks of age. (G+/+, R-/-) retinas that express only the mutant rhodopsin develop normal rod outer segments and show minimal rod cell loss even at 1 year of age. We conclude that G90D is constitutively active in mouse rods in vivo but that it does not cause significant rod degeneration. Instead, G90D desensitizes rods by a process equivalent to light adaptation.

A proximal retinal component in the primate photopic ERG a-wave.

PURPOSE: The monkey photopic ERG was studied during administration of glutamate analogs to determine whether the photopic a-wave derives exclusively from photoreceptors. METHODS: Monkey photopic ERGs were elicited using 200-msec flashes or 30-microseconds xenon photostrobe flashes on a steady light-adapting background of 40 cd/m2 (3.3 log scotopic troland). Intravitreal injections of APB, PDA, or both were given to block transmission to depolarizing and hyperpolarizing second-order retinal neurons, respectively. RESULTS: After injecting PDA to block light responses of horizontal cells and hyperpolarizing bipolar cells, part of the photopic a-wave was eliminated. The PDA-sensitive component, presumed to be due to activity postsynaptic to cones, was responsible for the photopic a-wave threshold and dominated the response over the initial 1 to 1.5 log units of intensity. For brighter stimuli, this component made a constant contribution to the photopic a-wave. A non-PDA-sensitive contribution to the a-wave, presumed to originate directly from cones, was first evident 1 to 1.5 log units above photopic a-wave threshold. It progressively dominated the a-wave at higher intensities, particularly at early time points after the flash. Injecting PDA almost eliminated the photopic a-wave elicited with bright xenon photostrobe flashes that are commonly used for human clinical ERG diagnostic testing, indicating that this a-wave may contain significant postreceptoral activity. CONCLUSION: The primate photopic ERG a-wave derives, in part, from retinal activity postsynaptic to cone photoreceptors, particularly for stimuli near the photopic ERG threshold that are typically used for human clinical studies.

Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degeneration.

PURPOSE: The aged Royal College of Surgeons (RCS) rat with advanced retinal degeneration loses the b-wave and shows a negative-going corneal electroretinogram (ERG) that has been attributed to loss of inner retinal function because of glutamate toxicity. The authors investigated the origin of this negative ERG and evaluated inner retinal function in late-stage RCS degeneration. METHODS: The ERG a-wave, b-wave, and scotopic threshold response (STR) were used to follow degeneration in RCS dystrophic animals between 18 and 120 days of age. Glutamate analogs were given by intravitreal injection to suppress transmission from photoreceptors to second- and third-order neurons to identify the origin of the negative ERG observed in older RCS dystrophic rats. RESULTS: In RCS dystrophic animals, the ERG developed normally up to day 27, but thereafter a- and b-wave sensitivity deteriorated more rapidly than the STR. By day 60, the STR threshold was elevated only 1 log unit, whereas a- and b-wave thresholds were > 2 log units higher than in controls. The STR range in dystrophic rats extended to brighter intensities previously dominated by the b-wave. Glutamate analogs eliminated the STR as well as the entire negative-going ERG in older dystrophic rats. CONCLUSIONS: The negative ERG in older RCS dystrophic rats originates in the inner retina and not from photoreceptors. Inner retinal signaling remains sensitive despite major photoreceptors loss in RCS rats, consistent with previous psychophysical findings. The b-wave may not be as useful as the STR in detecting loss of quantal catch in degenerating retinas. The ERG provides no evidence of glutamate excitotoxic damage to neurons postsynaptic to degenerating RCS photoreceptors.

The melatonin antagonist luzindole protects retinal photoreceptors from light damage in the rat.

PURPOSE: Systemic administration of melatonin can increase retinal light damage in the rat. The role of retinal melatonin receptors in modulating light-damage susceptibility was investigated by intravitreally injecting the melatonin receptor antagonist luzindole into rats. METHODS: Nine Sprague-Dawley albino rats 8 to 9 weeks of age were kept in 50 lux cyclic light for at least 7 days before receiving an intravitreal injection of 1 microl 1 mM luzindole in one eye and 1 microl vehicle in the other eye. The injection was given just before the beginning of the normal 12-hour dark phase. At the end of this dark period, animals were exposed to constant light of 2500 lux for 48 hours. Animals were returned to dim cyclic light for 7 days, and dark-adapted electroretinograms (ERGs) were then recorded from the two eyes simultaneously. The eyes were processed for retinal morphology. Photoreceptor nuclei were counted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measured at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but received no injections. RESULTS: Luzindole-treated eyes had ERG b-wave thresholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m2 lower than the fellow eyes injected with vehicle (P < 0.001), and the maximum b-wave amplitude was 1.0 +/- 0.2 log microV greater in luzindole-treated eyes (P < 0.001). Thresholds of the scotopic threshold response were 0.5 +/- 0.1 log cd/m2 lower than those in vehicle-injected eyes (P < 0.05). Luzindole-treated eyes on average had twice as many photoreceptor cells remaining (P < 0.005). In some areas, several rows of photoreceptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments. CONCLUSIONS: Eyes pretreated with the melatonin receptor competitive antagonist luzindole before the dark phase preceding constant light exposure were substantially protected from light damage to the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibility.

Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina.

PURPOSE: To investigate the possibility that previously demonstrated reductions in photoreceptor sensitivity to light in n-3 fatty-acid-deficient rats can be explained by alterations in rhodopsin content and/or function. METHODS: Sprague-Dawley rats were reared throughout gestation, lactation, and up to 24 weeks of age on a diet containing safflower oil (n-3 fatty-acid-deficient) or soybean oil as the sole source of lipids. Dark-adapted content and in vivo regeneration of rhodopsin after bleaching were measured by detergent extraction. The regeneration rate constants and number of photons absorbed by rhodopsin under steady-state bleach conditions were calculated from these values. The rate of metarhodopsin II (MII) formation in vitro was determined by flash bleaching extracted pigment and native rod outer segment membranes. Rod outer segment length and photoreceptor cell density were determined in histologic sections through the inferior central retina. RESULTS: Dark-adapted rhodopsin content of retinas from rats reared on safflower oil was 12% to 15% higher than that of rats raised on soybean oil at every age measured. The rate of rhodopsin regeneration was significantly slower in rats reared on safflower oil while the level of steady-state bleach was the same. This meant that the rats reared on safflower oil absorbed about one half as many photons during light exposure. The rate of metarhodopsin II formation in vitro was unaffected by n-3 fatty acid deficiency. No difference in either rod outer segment length or cell number was detected. CONCLUSION: A reduced capacity for photon absorption by rhodopsin could play a role in lowering retinal sensitivity to light in n-3 fatty-acid-deficient rats.

Human melanoma-associated retinopathy (MAR) antibodies alter the retinal ON-response of the monkey ERG in vivo.

PURPOSE: Melanoma-associated retinopathy (MAR) is a paraneoplastic condition that causes visual symptoms of night-blindness and photopsias. The electroretinogram (ERG) of MAR patients is characteristically abnormal in a way that implicates retinal depolarizing bipolar cell (DBC) dysfunction. Whether an injection of IgG from MAR patients into the vitreous of monkeys would alter the ERG acutely as a demonstration of a functional basis for patients' visual symptoms was explored. METHODS: MAR IgG was isolated from three visually symptomatic melanoma patients. Control IgG was from melanoma patients with no vision problems. The ERG was monitored after intravitreal injections into monkey eyes. One eye was injected with 2-amino-4-phosphonobutyric acid (APB), which is known to block DBC ON-pathway responses. Retinal immunocytochemistry was performed using fluorescein isothiocyanate-labeled goat anti-human IgG. RESULTS: Within 1 to 3 hours after MAR IgG injection, the ERG photopic b-wave was diminished, with far less effect on the a- and d-waves. These changes are characteristic of DBC dysfunction and were similar to the effects of APB. The scotopic ERG b-wave, which reflects activity of rod-driven DBCs, showed a loss of amplitude and threshold sensitivity after MAR IgG. Retinal immunocytochemistry with anti-IgG antibody showed IgG penetration throughout the retinal layers, but staining was not specific for a single type of retinal neuron. CONCLUSIONS: Intravitreal injection of human MAR IgG altered the monkey ERG acutely in ways that implicate functional disruption of retinal DBC signaling. These results support the hypothesis that MAR IgG circulating antibodies are responsible for the reported visual symptoms. Bipolar cells in the ON-pathway appear to be affected more than OFF-pathway bipolar cells of the cone pathway in this acute preparation.

The effect of calcium channel blocker diltiazem on photoreceptor degeneration in the rhodopsin Pro213His rat.

PURPOSE: To determine whether the calcium channel blocker D-cis-diltiazem promotes photoreceptor survival in rats with the Pro23His rhodopsin mutation. METHODS: Heterozygous Pro23His rhodopsin line 1 rats (n = 11) were treated daily, according to a protocol applied successfully in rd mice, with D-cis-diltiazem hydrochloride increased incrementally from 21 to 54 mg/kg in a divided dose (8 AM and 8 PM) administered by intraperitoneal (i.p.) injection for 21 days, beginning on days of age 10 through 12. Saline-treated line 1 rats (n = 6) received i.p. injections of an equal volume of 0.9% saline. Analysis on day 35 of age included dark-adapted corneal electroretinogram (ERG) b- and a-waves recorded from threshold to 0.63 log candela-seconds [cd-s]/m2, saturated a-waves elicited with a 2.1 log cd-s/m2 flash, and morphometry of the outer nuclear layer (ONL) and rod outer segments (ROS). RESULTS: ONL width and cell counts of diltiazem-treated and saline-treated animals at 35 days were reduced to 64%-68% of 15-day-old untreated P23H line 1 retinas. No photoreceptor rescue was found by measuring ONL width (P = 0.84), cell count (P = 0.42), or ROS length (P = 0.85). Functional assays by ERG b-wave threshold (P = 0.57), b-wave maximum amplitude (P = 0.46), and saturated a-wave amplitude (P = 0.59) also showed no rescue. CONCLUSIONS: D-cis-Diltiazem did not rescue photoreceptors of Pro23His rhodopsin mutation line 1 rats treated according to the protocol used in rd mouse.

Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats.

PURPOSE: To investigate possible protective effects of lens epithelium-derived growth factor (LEDGF) against photoreceptor death in light-damaged, Royal College of Surgeons (RCS) and P23H rhodopsin transgenic rats. METHODS: Twelve-week-old Sprague-Dawley (SD), 6-week-old RCS, and 10-day-old P23H (line 1, heterozygote) rats received an intravitreal injection of LEDGF fused with glutathione-S-transferase (GST-LEDGF). Fellow eyes received vehicle and served as control specimens. Two days after the injections, the SD rats were exposed to light of 2000 lux for 48 hours. Corneal Ganzfeld ERGs were recorded 10 days after light damage, at 10 weeks of age in RCS rats, and at 4 weeks of age in P23H rats. The eyes were then processed for histologic analysis. Heat shock protein (hsp) content in the sensory retina was analyzed quantitatively by protein immunoblot. RESULTS: In light-damaged rats, the ERG indicated retinal protection in GST-LEDGF-injected eyes, with b-wave and STR thresholds being 1.14 +/- 0.50 (mean +/- SD) and 0.60 +/- 0.26 log candela (cd)/m2 lower, respectively, than in vehicle-injected eyes (P < 0.01). The GST-LEDGF-treated eyes had maximum b-wave amplitudes that were significantly larger (P < 0.0005), had more than twice as many remaining photoreceptors, and had better organized outer segments than the control eyes. In RCS rats, the treated eyes had 2.76 +/- 0.73 and 0.83 +/- 0.09 log cd/m(2) lower thresholds for the b-wave and STR, respectively (P < 0.005), and had significantly larger maximum b-wave amplitude (P < 0.0005). GST-LEDGF-treated eyes of RCS rats also had more photoreceptors remaining (P < 0.005) and a thinner debris layer than control eyes. In P23H rats, GST-LEDGF treatment did not protect either retinal function or structure. The retinas from GST-LEDGF-treated eyes of SD and RCS rats had higher levels of hsp25 and alphaB-crystallin than vehicle-injected eyes. CONCLUSIONS: GST-LEDGF protects photoreceptor structure and function in both light-damaged and RCS rats. The increased expression of hsp25 and alphaB-crystallin may play a role in this protection. The absence of rescue in P23H raises the possibility that some forms of inherited retinal degeneration may not be amenable to treatment by intraocular injection of LEDGF.

P23H rhodopsin transgenic rat: correlation of retinal function with histopathology.

PURPOSE: To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa. METHODS: P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling. RESULTS: Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal. CONCLUSIONS: The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.

Trauma and other noninfectious problems in homosexual men.

Homosexual men are at risk for problems unique to their sexual orientation, and the management of even standard problems must often be altered. The recognition and management of problems related to the anorectum, breasts, and external genitalia in homosexual men are discussed.

Epidemiology of participation: an Australian community study.

STUDY OBJECTIVE: To determine the levels of participation in social and civic community life in a metropolitan region, and to assess differential levels of participation according to demographic, socioeconomic and health status. To contribute to policy debates on community participation, social capital and health using these empirical data. DESIGN: Cross sectional, postal, self completed survey on health and participation. SETTING: Random sample of the population from the western suburbs of Adelaide, the capital city of South Australia, a population of approximately 210 000. PARTICIPANTS: 2542 respondents from a sample of 4000 people aged 18 years and over who were registered on the electoral roll. MAIN RESULTS: The response rate to the survey was 63.6% (n=2542). Six indices of participation, on range of social and civic activities, with a number of items in each, were created. Levels of participation were highest in the informal social activities index (46.7-83.7% for individual items), and lowest in the index of civic activities of a collective nature (2.4-5.9% for individual items). Low levels of involvement in social and civic activities were reported more frequently by people of low income and low education levels. CONCLUSIONS: Levels of participation in social and civic community life in an urban setting are significantly influenced by individual socioeconomic status, health and other demographic characteristics. An understanding of the pattern of participation is important to inform social and health policy making. Increasing levels of participation will reduce social exclusion and is likely to improve the overall quality of community life.

Generalist health and welfare workers' response to alcohol related problems: role legitimacy and the need for role-support, an example from an Australian rural community.

In relating measures of therapeutic commitment (TC) in a sample of Australian rural town generalist health and welfare workers to their urban counterparts (modelled on Cartwright's study) it was confirmed that the former lacked the knowledge, training and support required to function as effective interventionists in alcohol related problems. Rural generalists were worse off than urban generalists when it came to gaining greater access to the variables that predict a positive TC.

Objectives perceived by administrators within the 'decision to divert network': conflict and resolution.

The objectives involved in the process of diversion as perceived by the administrators of two independent 'decision to divert networks' were examined. These networks were at different stages of their development. The older City network had passed through the trauma of complete breakdown and reorganisation, in which the interdependent goals of court and clinic (provision of a diagnostic advisory service to aid the court in sentencing and enhancement of the individual offenders' opportunities to select appropriate treatment where necessary) were stressed. Acceptance of these goals by justice and health personnel overlaid the previous polarity of opinion on the major issues of voluntaryism, confidentiality of information etc. Data on the more recently initiated Northern Beach network was similar to the pre-reorganisation City data, indicating that we could be facing a set of common problems during initial attempts to translate the principles of diversion into hard practice. The reorganisation of the clinical/correctional interface to formalise the role of the linkage worker, was seen to be effective in maintaining the 'Decision to divert' network in functioning order. However, at least one major area of potential conflict remains. This concerns the large discrepancy between Justice and Health expectancies in regard to the results of diversion. Justice personnel are inclined to expect that diversion will 'cure' addiction while health workers settle for far more modest goals.

Increased phase lag of the fundamental harmonic component of the 30 Hz flicker ERG in Schubert-Bornschein complete type CSNB.

The 30 Hz flicker electroretinogram (ERG) response was studied in seven patients with Schubert-Bornschein complete-type congenital stationary night blindness (SB-CSNB) by measuring conventional peak implicit times and by harmonic analysis. Responses were elicited with xenon photostrobe flashes. The fundamental flicker component showed a significant increased phase lag (P = 0.002), even though the peak implicit times were not delayed (P = 0.22). Although others have noted a "squared-off" flicker waveform in SB-CSNB, this is the first quantitative demonstration of a temporal abnormality in the flicker ERG and is the first report that a retinal disease can delay the fundamental flicker harmonic while the peak implicit time remains normal. Similarly, the phase of the flicker fundamental harmonic in monkey was also delayed after intravitreal 2-amino-4-phosphonobutyric acid (APB) that blocks the activity of depolarizing bipolar cells (DBC), whereas peak implicit time remained virtually unchanged. These observations, coupled with the normal amplitude and slope of the photopic a-wave (which was recorded under conditions that elicit a substantial contribution from hyperpolarizing bipolar cells) supports the hypothesis that the abnormality in the DBC pathway in SB-CSNB lies post-synaptic to the cones and not in the presynaptic glutamate release by cone photoreceptors.

Development of a questionnaire to examine the role of counsellors working with school students and their families with alcohol or other drug-related problems.

The Role Perception Questionnaire (RPQ) was developed to measure the perceptions of school-based counsellors who work with students or their families with alcohol, tobacco or other drug-related problems. The Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ) was used as a guide in developing the RPQ. This paper addresses the conceptual development, factor structure and internal reliability of this new questionnaire. Content and face validity were examined using expertise from the field. Statistical analysis of the 47 items resulted in the identification of four factors (sub-scales) described as Role Adequacy, Role Support, Role Perception and Role Definition. Recommendations are made for further development of the questionnaire and its use as a tool for assessing training needs for those who work with young people in schools.

Active surveillance of birth defects among U.S. Department of Defense beneficiaries: a feasibility study.

Since the Vietnam War, concern regarding the association of military exposures and birth defects has grown. The possibility of such associations remains a source of unease. To determine if such an association exists, birth defects surveillance among military families must be conducted. This project compared health record abstraction (active surveillance) with screening of Department of Defense electronic medical data (passive surveillance) to detect birth defects among San Diego County military families during the period January 1, 1997, through June 30, 1998. A total of 171 of 5,351 infants (3.2%) were identified as having a major defect, consistent with national civilian rates. There was approximately 80% concurrence between passive and active surveillance birth defect data, suggesting that a hybrid system of electronic data, supplemented with active surveillance in a specific region, represents a feasible and cost-effective surveillance program for the geographically dispersed military population.

The association of blisters with musculoskeletal injuries in male marine recruits.

A prospective study examining the epidemiology of blisters and, in particular, the association of blisters with subsequent injuries was conducted involving 2,130 male US Marine Corps recruits participating in initial physical training at the Marine Corps Recruit Depot in San Diego, California. From January 1993 through September 1994, recruits experienced an incidence of 2.05 blisters per 100 recruit-months. Recruits with blisters were 50% more likely to experience an additional training-related injury. Blisters, in combination with other related injuries, resulted in 159 clinic visits, 103 days of assigned light duty, and 177 lost days of training. This loss of time cost a minimum of $29,529. Extrapolating to the annual population of recruits, this represents an approximate annual expense of $690,000. Aggressive blister prevention and management in this setting has the potential to greatly reduce morbidity and fiscal costs.