Ninety-day and one-year healthcare utilization and costs after knee arthroplasty.

OBJECTIVES: This study examined ninety-day and one-year postoperative healthcare utilization and costs following total knee arthroplasty (TKA) from the health sector and patient perspectives. DESIGN: This study relied on: 1) patient-reported medical resource utilization data from diaries in the Knee Arthroplasty Pain Coping Skills Training (KASTPain) trial; and 2) Medicare fee schedules. Medicare payments, patient cost-sharing, and patient time costs were estimated. Generalized linear mixed models were used to identify baseline predictors of costs. RESULTS: In the first ninety days following TKA, patients had an average of 29.7 outpatient visits and 6% were hospitalized. Mean total costs during this period summed to $3,720, the majority attributed to outpatient visit costs (84%). Over the year following TKA, patients had an average of 48.9 outpatient visits, including 33.2 for physical therapy. About a quarter (24%) of patients were hospitalized. Medical costs were incurred at a decreasing rate, from $2,428 in the first six weeks to $648 in the last six weeks. Mean total medical costs across all patients over the year were $8,930, including $5,328 in outpatient costs. Total costs were positively associated with baseline Charlson comorbidity score (P < 0.01). Outpatient costs were positively associated with baseline Charlson comorbidity score (P = 0.03) and a bodily pain burden summary score (P < 0.01). Mean patient cost-sharing summed to $1,342 and time costs summed to $1,346. CONCLUSIONS: Costs in the ninety days and year after TKA can be substantial for both healthcare payers and patients. These costs should be considered as payers continue to explore alternative payment models.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Daily salivary cortisol patterns in midlife women with hot flashes.

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.

MsFLASH participants' priorities for alleviating menopausal symptoms.

OBJECTIVE: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). METHODS: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. RESULTS: The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. CONCLUSIONS: Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.

Self-reported menopausal symptoms in a racially diverse population and soy food consumption.

OBJECTIVES: Evaluate the association of self-reported vasomotor symptom (VMS) frequency with race/ethnicity among a diverse midlife US population and explore menopause symptom differences by dietary soy isoflavone (genistein+daidzein) consumption. STUDY DESIGN: Cross-sectional population-based study of peri- and postmenopausal women, ages 45-58. OUTCOMES: Recent VMS frequency, VMS ever; recent symptom bother (hot flashes, night sweats, headache and joint-ache). RESULTS: Of 18,500 potentially eligible women, 9325 returned questionnaires (50.4% response); 3691 were excluded (premenopausal, missing data, taking hormones). Of 5634 remaining women, 82.1% reported hot flashes ever, 73.1% reported night sweats ever; 48.8% and 38.6% reported recent hot flashes or night sweats, respectively. Compared with White women, Chinese, Japanese, Vietnamese, other Asian (each p<0.001) and Filipino (p<0.01) women less commonly reported ever having hot flashes; Asian women less commonly reported recent VMS bother (p<0.001). Black women more commonly reported hot flashes ever (p<0.05) and recent VMS bother (p<0.05). Compared with non-Hispanic White women, Hispanic women were less likely to report hot flashes (p<0.05) or night sweats (p<0.001) ever. Women were classified by isoflavone consumption: (1) none (n=1819), (2) 0.01-4.30 mg/day (n=1931), (3) 4.31-24.99 mg/day (n=1347) and (4) ≥ 25 mg/day (n=537). There were no group differences in recent VMS number/day: (1) 7.0 (95% CI 6.5, 7.5); (2) 6.4 (95% CI 6.0, 7.1); (3) 7.0 (95% CI 6.3, 8.2); and (4) 6.8 (95% CI 6.1, 7.7). CONCLUSIONS: Menopausal symptoms, independent of isoflavone intake, varied considerably by race/ethnicity and were least common among Asian races.

Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective?

BACKGROUND: Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. METHODS: A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. RESULTS: The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. CONCLUSIONS: Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug.

Pre-clinical toxicity assessment of tumor-targeted interleukin-12 low-intensity electrogenetherapy.

This study's goal was to assess the safety of tumor-targeted interleukin-12 (ttIL-12) when administered by electrogenetherapy in C3H/HeJ mice by identifying an initial safe dose for human dose escalation schemes, toxicity target organs, markers of toxicity, and toxicity reversibility. Tumor-free mice receiving two doses of 0.45% NaCl, 1 µg ttIL-12 DNA in 0.45% NaCl or 5 µg ttIL-12 DNA in 0.45% NaCl, 10 days apart combined with low-intensity electroporation were compared with non-treatment controls over time. All mice had blood cell counts, serum chemistry profiles, plasma interleukin-12 and IFNγ determinations, necropsy and multi-organ histopathology. Mild treatment-associated changes included electroporation-associated muscle changes that resolved by 30 days; decreased total white blood cell counts and infectious disease in the 5 µg ttIL-12 group, but not in the 1 µg group, and liver changes in ttIL-12 groups that correlated with alanine transaminase levels and resolved by 30 days. Dystrophic cardiac calcification seen in older, 5 µg ttIL-12-treated mice was the only serious toxicity. Based on these results and the lack of any effect on wound healing when combined with surgery, low-intensity electrogenetherapy with ttIL-12 appears to be safe and well tolerated.

Factors associated with non-compliance with hormone therapy cessation before screening mammography.

OBJECTIVES: To evaluate factors associated with non-compliance with discontinuation of hormone therapy (HT) within a study on the effect of HT cessation on mammography performance. METHODS: This randomized, controlled trial was conducted at Group Health, a health plan in Washington State, USA. Eligibility included: age 45-80 years; due for screening ('study') mammogram; and prior screening mammogram while using HT. We randomized 1704 women to no cessation (n = 567), 1-month (n = 570), or 2-month cessation (n = 567), and called participants before cessation to review instructions. We collected self-reported data at randomization (baseline) and before the study mammogram, including symptoms and compliance. This analysis includes women randomized to 1-month or 2-month cessation with complete baseline and follow-up questionnaires (n = 883). RESULTS: Most participants were using unopposed estrogen (63.3%) and intended to continue HT (90%); 9.6% were non-compliant with HT cessation. Comparing 2-month vs. 1-month cessation, the age and body mass index (BMI)-adjusted relative risk (RR) for non-compliance was 1.72 (95% confidence interval (CI) 1.12-2.60). Baseline variables associated with non-compliance included: age ≤55 vs. >55 years (RR 2.34; 95% CI 1.34-4.41); BMI < 25 vs. BMI ≥30 kg/m 2 (RR 1.63; 95% CI 1.01-2.63); unopposed estrogen vs. estrogen plus progestin (RR 1.59; 95% CI 1.01-2.51); using HT to manage sleep (RR 1.80; 95% CI 1.20-2.71); severe vs. no night sweats (RR 1.68; 95% CI 1.03-2.74); and night sweats that interfered with sleep (RR 1.78; 95% CI 1.02-3.11). CONCLUSIONS: Non-compliance with HT cessation before screening mammogram was associated with younger age, lower BMI, symptom severity and use of unopposed estrogen. Alternatives for menopause symptom management are needed to assist women with HT cessation.

Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs.

On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs.

On the basis of superior outcomes from electrochemogene therapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12 DNA (fIL-12 DNA) injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform. It was associated with repair of bone lysis in cured dogs, it improved quality of life of dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Leiomyoma characteristics and risk of subsequent surgery after myomectomy.

OBJECTIVE: Evaluate the association between leiomyoma characteristics at myomectomy with subsequent surgery risk. METHODS: A population-based nested case control study from a cohort of women at a large HMO, identified as having had a myomectomy was performed; 82 cases had subsequent uterine surgery; 82 controls, frequency matched for age and date of first surgery, did not. Medical records were abstracted; follow-up was 18-128months. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated. RESULTS: Women without subserosal myomas were more likely to have a second surgery as compared to women with at least one subserosal myoma, aOR=4.1(95% CI 1.5-10.9). Size of myomas did not predict subsequent surgery in subanalyses by type of surgery. Number of leiomyomas was not predictive of a subsequent uterine surgery overall or in subgroup analyses. CONCLUSION: Myoma location, but not number or size, impacts the risk for subsequent leiomyoma uterine surgery.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals.

BACKGROUND AND PURPOSE: Most analyses of intravenous tissue plasminogen activator (IV tPA) use for acute stroke in routine practice have been limited by sample size and generally restricted to patients treated in large academic medical facilities. In the present study, we sought to estimate among community hospitals the use of IV tPA and to identify factors associated with the use of IV tPA and inpatient mortality. METHODS: We evaluated a retrospective cohort of 23 058 patients with ischemic stroke from 137 community hospitals. RESULTS: Three hundred sixty-two (1.6%) patients were treated with IV tPA, and 9.9% of those patients died during the hospitalization period. In 35.0% of the hospitals, no patients were treated with IV tPA, whereas 14.6% of hospitals treated approximately 3.0% with IV tPA. After control for multiple factors, younger patients, more severely ill patients (OR 2.02, 95% CI 1.36 to 3.01), and patients treated in rural hospitals (OR 1.80, 95% CI 0.99 to 3.26) were more likely to receive IV tPA, whereas black patients were less likely (OR 0.54, 95% CI 0.31 to 0.95). There also was a trend showing that women were less likely to receive IV tPA (OR 0.84, 95% CI 0.69 to 1.03). Factors associated with an increased odds of inpatient mortality included receipt of IV tPA among men (OR 2.81, 95% CI 1.72 to 4.58) and increased age. Black patients were 27% less likely to die during hospitalization (95% CI 0.60 to 0.90). CONCLUSIONS: In this large, retrospective evaluation of community hospital practice, the use IV tPA and inpatient mortality rates among IV tPA-treated patients were consistent with those of other studies. The likelihood of receiving IV tPA varies by race, age, disease severity, and possibly gender. These factors may influence mortality rates.

Inpatient costs, length of stay, and mortality for cerebrovascular events in community hospitals.

BACKGROUND: Accurate estimates of inpatient cost, length of stay (LOS), and mortality are necessary for the development of economic models to estimate the cost-effectiveness of stroke-related treatments. Estimates based on data from academic institutions may not be generalizable to community hospitals. In this study, the authors estimated inpatient costs, LOS, and in-hospital mortality for patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic cerebral infarction (ICI), and TIA who were treated in community hospitals. METHODS: The authors selected patients using International Classification of Diseases-9-Clinical Modification primary diagnosis codes from the HBSI EXPLORE database. They analyzed patient-level data and inpatient costs, derived from detailed utilization data, for all patients admitted to 137 community hospitals in 1998. Multivariate statistical techniques were used to examine patient-, hospital-, and outcome-related factors associated with inpatient costs. RESULTS: Patients with SAH incurred the highest average cost ($23,777, n = 1,124), followed by patients with ICH ($10,241, n = 3,139), ICI ($5,837, n = 18,740), and TIA ($3,350, n = 7,861). Patient subgroups ranked in the same order for average LOS at 11.5 days for SAH, 7.5 days for ICH, 5.9 days for ICI, and 3.4 days for TIA. Almost one third of patients with SAH (29.0%) and ICH (33.1%) died during hospitalization, whereas 7.0% with ICI and 0.2% with TIA died. For each event, as patient age increased, average costs consistently decreased. Also, average costs were higher among patients treated in community teaching hospitals compared to community nonteaching hospitals for each cerebrovascular event (10 to 29%). CONCLUSIONS: Inpatient costs, LOS, and mortality for patients with cerebrovascular disease are dependent on patient and hospital characteristics.

Antibiotic treatment of tuboovarian abscess: comparison of broad-spectrum beta-lactam agents versus clindamycin-containing regimens.

One hundred nineteen patients with tuboovarian abscess were evaluated for response to antibiotics. Results were stratified into three groups by antimicrobial regimen. Group 1 consisted of 37 patients treated with a single-agent broad-spectrum intravenous antibiotic and oral doxycycline. Initial clinical response (defined as decreased pain, diminished white blood cell count, or defervescence) in group 1 was 31/37 (84%). Group 2 consisted of 64 patients treated with clindamycin in combination with an aminoglycoside with or without a penicillin. There was an initial clinical response in 45 of 64 (70%). Group 3 consisted of 18 patients from group 1 who were changed to a clindamycin-containing regimen after 2 to 3 days of initial treatment with a single-agent broad-spectrum antibiotic. The decision to switch antibiotics was not based on treatment failure but occurred when delayed ultrasonography confirmed the diagnosis of tuboovarian abscess. The switch reflected physician preference for clindamycin-containing regimens in the treatment of tuboovarian abscesses. The response rate in this subset of patients was 14 of 18 (78%). Overall initial clinical response rate was 90 of 119 (75%). There were no statistically significant demographic or clinical differences among the three groups. There was no statistical difference in the rate of early and late antibiotic failure rates among the groups. Our study demonstrates that extended-spectrum antibiotic coverage, including single-agent broad-spectrum antibiotics such as cefoxitin, in conjunction with doxycycline has efficacy that is equivalent to that of clindamycin-containing regimens. An overall medical treatment success rate of 75% suggests that conservative treatment of tuboovarian abscesses is warranted.

Fecal proteolytic activity in clinically normal cats and in a cat with exocrine pancreatic insufficiency.

Fecal proteolytic activity determined in single samples collected on each of 3 consecutive days from each of 20 clinically normal cats ranged from 19 to 363 azocasein units (ACU)/g of feces when determined colorimetrically, using azocasein substrate, and ranged from undetectable (in 1 sample from 1 cat) to 21 mm of gel-clearing when determined using radial enzyme diffusion in agar gels containing a casein substrate. Corresponding mean 3-day values for each cat ranged from 29 to 207 ACU/g and from 5 to 16 mm, respectively. Studies of proteolytic activity remaining after treatment of fecal extracts with a specific trypsin inhibitor indicated that trypsin accounted for 0 to 77% of proteolytic activity. In a cat with exocrine pancreatic insufficiency, fecal proteolytic activity was 0, 0, and 3 ACU/g in a sample of feces collected from each of 3 consecutive days and was undetectable by use of radial enzyme diffusion. Assay of fecal proteolytic activity by use of either azocasein hydrolysis or radial enzyme diffusion allows evaluation of pancreatic function in cats, provided that several samples of feces are tested.

Cardiovascular asymmetries and cardiac perception.

Two strategies for evaluating the lateral specificity of cardiac sensory innervation were reviewed: (1) electrophysiological recording of cardiac-relevant cortical activity; and (2) behavioral assessment of right versus left differences in cardiac sensory perception. Electrophysiological data from two different laboratories suggest strongly that there is a link between cardiac events and cortical response to stimulation, but only for the right hemisphere. Two experiments from our laboratory suggest that there is a complex relationship among cerebral lateral preference, assessed by conjugate lateral eye movements, arousal, and individual differences in accuracy of self-perception of heart beats. The data, overall, suggest that the right hemisphere is involved specifically in heartbeat perception.

Chromosomal abnormalities associated with congenital contractures (arthrogryposis).

In a study of 350 patients with multiple congenital contractures (arthrogryposis), 80 (23%) patients had mental retardation or were developmentally delayed. Out of that group of 80 patients, 13 (16%) were found to have abnormal karyotypes. Two of the thirteen had a family history of chromosomal abnormalities without congenital contractures, therefore, 11 patients had chromosomal anomalies which appeared to be associated with the congenital contractures. Five of the eleven (45%) had chromosome mosaicism, three of those had tissue mosaicism. Two had abnormal skin fibroblast cell lines and normal peripheral leukocyte chromosome studies and one had a normal bone marrow karyotype with abnormal peripheral leukocyte chromosome studies. Chromosome studies were done in these patients with congenital contractures because of developmental delay and multisystem involvement, or recognition of clinical features typical of a chromosomal syndrome. We recommend first lymphocyte; and if those are normal, then fibroblast studies be done on all patients with multiple joint contractures and developmental delay, particularly if unusual facial features or multisystem abnormalities are present.