Acquired pendular nystagmus: its characteristics, localising value and pathophysiology

Investigations were made of 16 patients with acquired pendular nystagmus and a further 32 cases reported in the literature were reviewed. Amongst our own patients two thirds had multiple sclerosis, almost one third a cerebrovascular accident or angioma and two had optic atrophy with squint. The nystagmus took forms which could be monocular or binocular, conjugate or disconjugate and could involve movements about single or multiple axes. Spectral analysis was used to characterise the amplitude and frequency of the movements and to estimate the degree of relationship (coherence) between movements of the two eyes or between movements of one eye about several axes. The oscillations ranged in frequency from 2·5 Hz to 6 Hz, with typical amplitudes between 3° and 5°. In a given patient all oscillations, regardless of plane, were highly synchronised. Somatic tremors of the upper limb, face and palate associated with the nystagmus were often at similar frequencies to the eye movement. The other ocular signs common to all our patients were the presence of squint with failure of convergence. Most patients also had skew deviation or internuclear ophthalmoplegia or both. The major oculomotor systems, that is, saccades, pursuit, optokinetic and vestibulo-ocular reflexes could be intact. It is inferred that the mechanism responsible for the pendular nystagmus lies at a level which is close to the oculomotor nuclei so that it can have monocular effects but is not part of the primary motor pathways. It is possible that this mechanism normally subserves maintenance of conjugate movement and posture of the eyes. The periodicity of the nystagmus is likely to arise from instability in a certain type(s) of neurone, for the associated somatic tremors have similar characteristics and yet involve very different neuronal muscular circuitry. Prognosis for cessation of the nystagmus is poor. In five patients with multiple sclerosis it was suppressed by intravenous hyoscine with, however, unacceptable subsequent side effects.     

The effect of an intermediate care unit on the demographics and outcomes of a surgical intensive care unit population

HYPOTHESIS: Many surgical intensive care units (SICUs) face bed shortages for acutely ill patients that may result from a large proportion of bed occupation by chronically ill patients. We hypothesized that the introduction of a new intermediate care or step-down unit (SDU) managed by surgically trained intensivists would allow the admission of more acutely ill patients while maintaining satisfactory outcomes. DESIGN: Prospective retrospective comparison of SICU patient populations before and after the introduction of an SDU. SETTING: The SICU of New York-Presbyterian Hospital, New York Weill Cornell Center, a university hospital containing a level I trauma center. PATIENTS AND INTERVENTIONS: All patients in the SICU admitted from August 1, 1996, through June 30, 1997, were SICU patients prior to the introduction of the SDU. Patients admitted from August 1, 1997, through June 30, 1998, were SICU post-SDU patients, and SDU patients included those admitted to the SDU from August 1, 1997, through July 1, 1998. MAIN OUTCOME MEASURES: For each of the 2 eras, patients were compared for age, sources of admission, Acute Physiology and Chronic Health Evaluation (APACHE) II and III scores, unit length of stay, and mortality. Other data collected included origin of admission, nature of admission, and diagnosis. RESULTS: Six hundred sixty-six patients were admitted during the pre-SDU era, while a total of 1117 patients (619 SICU and 498 SDU patients) were admitted in the post-SDU era. After the introduction of the SDU, the mean (standard deviation) APACHE II scores of the SICU and SDU patients increased (14.2 vs 13.4, P =.04) without affecting mortality (6.0% in the post-SDU era vs 8.2% in the pre-SDU era, P =.07). The post-SDU era had a higher proportion of emergency admissions (42.3% vs 48.6%, P<.05) and interhospital transfers (7% vs 1%). CONCLUSIONS: Opening an SDU resulted in a significant increase in the overall severity of the SICU population. Creation of an SDU managed by surgically trained intensivists may optimize the use of a hospital's resources, permit the expansion of emergency or tertiary care services, and improve outcomes for critically ill surgical patients.     

Causes and consequences of fever complicating critical surgical illness

BACKGROUND: Fever may have malign consequences in the postoperative period. This study was performed to determine the causes and consequences of fever in critically ill surgical patients. The specific hypothesis tested is that postoperative fever is associated with adverse clinical outcomes, including increased organ dysfunction and risk of death. METHODS: Inception-cohort study of critically ill surgical patients who manifested a core temperature of >/=38.2 degrees C for the first time. The episode of fever was monitored until resolution, which was defined as a core temperature of <38.2 degrees C for at least 72 consecutive h. Demographic data collected included age, gender, admission diagnosis, admission status (elective/emergency), severity of illness (APACHE III), the systemic inflammatory response syndrome (SIRS) score, the cumulative multiple organ dysfunction score, cause of fever (infectious/non-infectious), ICU and hospital length of stay, and mortality. The day of onset of fever in the ICU, peak temperature, ICU day of peak temperature, and duration of fever episode were recorded. All diagnostic and therapeutic interventions were recorded, including the type and duration of antibiotic therapy. Univariate results of possible significance (alpha < 0.15) were tested in logistic regression models for independence of effect upon mortality after auto-correlation was excluded by matrix correlations and the Durbin-Watson statistic. Cases where both non-infectious and infectious causes of fever were present were analyzed as part of the infectious group, whereas the cumulative MOD score was dichotomized (< 5, >/=5 points) at a value known to be associated with increased mortality. RESULTS: Among 2,419 screened patients, 626 patients (26%) developed fever. Febrile patients were older, sicker, more likely to have undergone emergency surgery, more likely to develop organ dysfunction, and more likely to die (all, p < 0.0001). The mean day of onset of fever was day 1 and the mean peak temperature for the episode was 39.1 +/- 0.1 degrees C. For most patients, it was their only episode of fever, with a mean of 1.4 +/- 0.1 episodes/patient. Forty-six percent of febrile patients were found to have an infectious cause of fever. Nearly all patients had SIRS, and nearly all developed organ dysfunction to some degree. By logistic regression, the presence of SIRS (as opposed to fever in isolation), emergency status, higher APACHE III score and the peak temperature were associated with increased mortality, with peak temperature being the most powerful predictor in the model (OR 2.20, 95% Cl 1.57-3.19). Gender had no bearing on outcome, and there was a trend toward a protective effect from an infectious etiology of fever. CONCLUSIONS: Postoperative fever is deleterious to critically ill patients. The magnitude of fever is a determinant of mortality, whereas an infectious etiology of fever may not be. The impacts of nosocomial infection and suppression of fever on critically surgical patients deserve further study.     

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.      

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

A STD/HIV prevention trial among adolescents in managed care

OBJECTIVE: To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors. DESIGN: A randomized intervention trial with 3- and 9-month follow-up. SETTING: Five staff-model managed care sites in Washington, DC (n = 19 pediatricians). PATIENTS: Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%). INTERVENTION: Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence). MAIN OUTCOME MEASURES: Adolescent-reported sexual intercourse and condom use. RESULTS: More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94). CONCLUSIONS: STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.     

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.     

A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial

Background  

Because of a high cardiovascular disease (CVD) risk in people with Familial Hypercholesterolemia (FH), early prevention of cardiovascular disease is important for health gain and cost reduction. This project focuses on the development and evaluation of an innovative intervention aiming to reduce CVD risk by promoting a healthy lifestyle among people with FH.