Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice

The multiple intestinal neoplasia (Apc(Min/+)) mouse possesses a germline mutation at codon 850 of the adenomatous polyposis coli (Apc) gene resulting in the formation of a nonfunctional truncated gene product. Following a somatic mutation of the remaining wild-type allele, mice spontaneously develop approximately 40-50 tumors throughout the intestinal tract. This mouse model has been used to study intestinal tumorigenesis because this mutation is analogous to the inherited APC mutation in humans with familial adenomatous polyposis (FAP). These individuals characteristically develop numerous adenomas throughout their intestinal tracts. Only a few studies have evaluated the effects of dietary fatty acids on tumorigenesis in this animal model with varying results, and none have linked these effects to alterations in arachidonic acid (AA) metabolism. This study was designed to evaluate the antitumorigenic effect of dietary (n-3) polyunsaturated fatty acids (PUFA) in the Apc(Min/+) mouse model and to determine whether these effects are related to inhibition of AA metabolism. Male Apc(Min/+)mice were fed diets supplemented with eicosapentaenoic acid (EPA), AA or a combination of AA + EPA. Mean tumor number in the EPA group was 68% lower (P<0.05) compared with the control group, whereas AA supplementation did not significantly alter tumor load. The reduction in tumor load coincided with significant reductions in intestinal AA content and levels of prostaglandins. However, supplementing AA to the EPA diet (AA + EPA) abolished the antitumorigenic effect of EPA, increased tissue AA content fourfold and prostaglandin production two- to fourfold. These results indicate that AA is involved in tumorigenesis and suggest that EPA's ability to reduce tumor load in Apc(Min/+) mice is related to reductions in tissue AA content or its metabolism.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

Seasonal variation of hip fracture at three latitudes

We studied the seasonal variation of hip fracture admissions at three different latitudes: Scotland (56 degrees North; 54,399 admissions); Shatin, Hong Kong (22 degrees North; 4180 admissions); and Auckland, New Zealand (36 degrees South; 2257 admissions). We calculated the extent of seasonal variation (amplitude) and the time of year of the peak value (acrophase) by fitting a sine curve to monthly data using cosinor analysis. A significant seasonal variation was found in all three countries, at a high level in Scotland (p < 0.01) and Hong Kong (p < 0.001), but just significant in New Zealand (p < 0.05). The extent of the seasonal change was very similar in Scotland and New Zealand, but, as expected, the peak in New Zealand (early September) was approximately six months ahead of Scotland (mid February). In Hong Kong, the amplitude was three times greater than in Scotland and the peak occurred a month earlier. There is neither snow nor ice in Hong Kong, and this provides powerful evidence against a major influence of conditions underfoot causing extra falls in winter. In Scotland there was a significant increase in the proportion of deaths in winter as compared to summer. The Scotland/Hong Kong amplitude difference is striking, but it is unknown whether this has a genetic or environmental explanation. The cause of seasonal death difference to a given injury is also unknown. Possible mechanisms are discussed, but the purpose is to report two new epidemiological features, without wild speculative hypotheses. The findings should be viewed as leads to further epidemiological, clinical and more basic research.     

Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DR). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (IG), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P>0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P<0.05), while DF removed more IgA (72 % vs. 21 %, P< 0.05) and IgM (89 % vs. 57 %, P<0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG. Received: 10 September 1999, Received in revised form: 7 February 2000, Accepted: 24 February 2000     

Quality of sleep and related factors during chemotherapy in patients with stage I/II breast cancer.

BACKGROUND: Insomnia causes severe distress in patients with breast cancer who receive chemotherapy. Few studies have focused on using objective methods to assess sleep. This study explored the quality of sleep and related factors in patients with breast cancer during chemotherapy. METHODS: The participants were 16 women with stage I or II breast cancer receiving their third cycle of chemotherapy with cyclophosphamide, epirubicin and fluorouracil, or cyclophosphamide, methotrexate and fluorouracil. The effects of chemotherapy on sleep were assessed on the 8th and 9th days of the third cycle, i.e. the active phase in terms of side effects, and the last 2 days before the start of the fourth cycle for comparison. Instruments used to assess sleep quality and related factors included actigraphy, the Hospital Anxiety and Depression Scale (HADS), the Symptom Distress Scale (SDS), the Fatigue Visual Analogue Scale (FVAS), the Epworth Sleepiness Scale (ESS), and sleep logs. RESULTS: During the active phase, patients showed an anxiety tendency with an average HADS score of 7.8 +/- 3.8. The average FVAS score was 4 +/- 2, indicative of mild fatigue, and SDS score (1.8 +/- 0.3) also indicated mild symptom distress. The number of awakenings each night was 2.2 +/- 1.6 by sleep logs, and the total time spent awake during these episodes was 47.8 +/- 26.1 minutes by Actiwatch. Sleep efficiency measured by Actiwatch in the active phase was 82.1 +/- 9.4% below the normal limit. Daytime sleepiness assessed by ESS showed mild sleepiness (6.0 +/- 3.5) in the active phase. CONCLUSION: The study showed poor sleep quality and daytime sleepiness in patients with breast cancer during the active phase of chemotherapy. Chemotherapy may bring symptom distress to patients and adversely influence sleep quality.     

Comparison of the costs and recovery profiles of three anesthetic techniques for ambulatory anorectal surgery

BACKGROUND: Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting. METHODS: Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision. RESULTS: The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%). CONCLUSIONS: The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.