Is stroke mortality on the decline in England?

This paper challenges the assumption that mortality from stroke will remain constant or decline over the next few decades. A decline in stroke mortality could be brought about by changes in factors acting close to the time of death (period effect) or by risk factors determined by the generation into which a person is born (cohort effect). Age-specific death rates for stroke (1931-1985) in England and Wales were analyzed to estimate the influence of these different effects. There were significant effects for age, period, and cohort on mortality from stroke with significantly different age and period effects in each sex. The effect of age was linear, with an increasing mortality with age in both sexes. Cohort analysis demonstrated a deceleration away from the previous trend in the mortality rates associated with birth cohorts born after 1880, followed by an acceleration in the trend of mortality rates in cohorts born after 1910. These relative increases in risk for cohorts born after 1910 were offset by a deceleration in mortality associated with periods from around 1951-1954. Since cohort effects are likely to be associated with a lifetime increase in risk of stroke mortality, it is difficult to predict the extent of any long-term fall in stroke incidence.     

In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3.

Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation with a replication-incompetent, genomic herpes simplex virus-based vector containing the coding sequence for neurotrophin-3 to transduce sensory neurons of the rat dorsal root ganglion in vivo, and found that expression of neurotrophin-3 from the vector protected peripheral sensory axons from neuropathy induced by intoxication with pyridoxine assessed by electrophysiological (foot sensory response amplitude, and conduction velocity, and H-wave), histological (nerve morphology and morphometry), and behavioral measures of proprioceptive function. In vivo gene transfer using herpes simplex virus vectors provides a unique option for treatment of diseases of the sensory peripheral nervous system.     

Desmethylimipramine promotes recovery of self-stimulation from the prefrontal cortex following footshock.

Intracranial self-stimulation (ICSS) was assessed from the prefrontal cortex in CD-1 mice immediately (0 h), 24 h and 168 h following exposure to uncontrollable footshock. Marked reductions in ICSS rates were observed in all mice immediately following the stressor. Although the ICSS alterations were transient in some animals, ICSS rates were reduced in the majority of animals 24-h and 168-h poststressor. Mice of either the shock or no shock treatment groups were administered either saline or desmethylimipramine (DMI, 5 mg/kg x 2) for 20 consecutive days. Chronic DMI ameliorated the stressor-induced ICSS deficits from the prefrontal cortex. Potential explanations for the stressor-provoked variations in ICSS and the effects of DMI are discussed.     

Zollinger-Ellison syndrome

As clinical experience with patients with ZES has grown, increasing recognition has been made of the broad spectrum of symptoms associated with gastrinomas. Diarrhea and acid-induced esophageal injury have taken their place alongside chronic peptic ulcer disease as indications for screening for gastrinoma. Diagnostic testing should begin with fasting serum gastrin levels and should include intravenous secretin infusion if fasting serum levels of gastrin are nondiagnostic and the patient is not found to be hypochlorhydric. Tumor localization is critical to aid in the identification of patients with potentially curable localized disease. Preoperative evaluation utilizing CT scanning with intravenous contrast should be done early and should be supplemented by other imaging modalities as necessary. Exploratory laparotomy, including a thorough examination of the duodenum and perhaps intraoperative ultrasound, should be performed in all patients with sporadic gastrinoma who lack evidence of extensive metastatic disease on preoperative evaluation. By utilizing this approach, it is likely that at least 20% of patients with ZES can be cured. With the availability of the highly effective H(+)-K(+)-ATPase inhibitor omeprazole, excellent control of symptoms related to gastric acid hypersecretion can be expected. Patients with unresectable gastrinoma may thus avoid potentially morbid antisecretory surgery and be managed with a fairly simple medical regimen. Further developments in the chemotherapeutic management of these patients with unresectable disease should be forthcoming in the future.     

Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study

The classification of breast parenchymal patterns (N1, P1, P2, DY) and the percentage of the breast containing radiographic densities are two highly correlated radiographic measures proposed as predictors of the risk of breast cancer. In this case-control study, 160 cases of breast cancer and 160 matched controls from a mammography referral practice were compared to determine the risk of breast cancer associated with each of these two radiographic measures. The mammographic densities were quantified on caudal projections by means of a compensating polar planimeter. A relative risk estimate of 3.3 (p less than .05) was associated with the P2 + DY patterns compared with the N1 + P1 patterns. Significantly elevated risks of 4.3 to 5.5 also were observed among women whose breasts contained at least 25% mammographic densities, compared with women with less than 25% involvement. These radiographic measures tended to be more predictive of the risk of breast cancer in black women than in white women. Although the precise clinical roles of breast parenchymal patterns and densities have not been defined fully, the results of this study suggest that they are useful in the recognition of women at high risk of breast cancer. We make no claims that the findings of this study are sufficiently developed to be used as a basis for screening strategies.     

Determinations of glucose turnover and oxidation in normal volunteers and septic patients using stable and radio-isotopes: the response to glucose infusion and total parenteral feeding

Rates of glucose turnover and oxidation were isotopically determined in normal volunteers (n = 16) and in severely septic patients (n = 10). Glucose turnover was determined using primed constant infusions of either 6-3H- or 6,6-d-glucose and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Basal rates of glucose turnover, oxidation, and plasma clearance were significantly higher in the septic patients than in the volunteers. During glucose infusion (4 mg/kg.min) endogenous glucose production was virtually abolished in the volunteers (94 +/- 4% suppression). There was significantly less suppression in the septic patients (39 +/- 7%); (P less than 0.01). In addition, the percentage of available glucose oxidized (i.e. the percentage of glucose uptake oxidized) was significantly less in the septic patients. When the patients were studied during total parenteral nutrition (at a similar rate of glucose infusion) there was no further suppression of endogenous glucose production compared with that seen during 2 h of glucose infusion. However, the percentage of available glucose oxidized increased significantly. From these studies it is concluded that septic patients continue to have ongoing consumption of host tissue despite receiving either glucose infusion or total parenteral nutrition, and septic patients are less able to oxidize glucose than normal volunteers when infused for only 2 h. However, adaptation occurs with the longer infusion time used in total parenteral nutrition (TPN).