Frederic A. Wyle

Circadian blood pressure patterns in ambulatory hypertensive patients: Effects of age

Circadian blood pressure monitoring was performed in 50 untreated ambulatory hypertensive patients to study the effects of age on the pattern and variability of blood pressure and heart rate. Casual blood pressure, measured in the morning, was greater than the average of the blood pressures measured at 7.5 minute intervals for 24 hours (148 +/- 2/95 +/- 2 and 137 +/- 2/88 +/- 2 mm Hg, p less than 0.001). The correlation between casual systolic pressure and the 24 hour average was stronger (p less than 0.05) in younger (less than 55 years of age) patients (r = 0.69, n = 24, p less than 0.001) than in older patients (r = 0.42, n = 26, p less than 0.1). Similarly, diastolic pressures correlated more strongly (p less than 0.05) in younger patients (r = 0.71, p less than 0.001) than in older patients (r = 0.43, p less than 0.05). Variability of systolic pressure, defined as the standard deviation of all readings obtained during 24 hours, was greater than that of diastolic pressure (16.7 and 13.1 mm Hg, respectively, p less than 0.001). Moreover, the variability of systolic pressure was greater in older than in younger patients (18.1 and 15.2 mm Hg, respectively, p less than 0.01). The variability of diastolic pressure was slightly but not significantly greater in older patients (13.7 and 12.5 mm Hg, not significant). The circadian pattern of blood pressure, expressed as averages of readings obtained during consecutive 2 hour intervals, was similar in the two age groups. However, the level of systolic pressure was consistently higher (p less than 0.01) and that of both diastolic pressure and heart rate consistently lower (p less than 0.01) in older patients. Thus, ambulatory circadian blood pressure monitoring reveals significant changes in blood pressure levels and its variability with age; the casual blood pressure does not accurately reflect these changes. Longer periods of blood pressure monitoring are required for accurate assessment of the characteristics of hypertension in the aged.

Maggot Therapy for Treating Pressure Ulcers in Spinal Cord Injury Patients

For centuries, maggot therapy (MT) has been recognized as an aid to wound healing. By including live blowfly larvae in wound dressings, earlier physicians noted thorough debridement which hastened wound healing. We initiated a prospective controlled study to evaluate the utility of maggot therapy for treating pressure ulcers in spinal cord injury patients in the modern era. Eight of our patients received MT after a baseline assessment of healing under conventional therapy (defined as any therapy prescribed by the patients primary care team). Surface area, tissue quality and healing rates were monitored weekly. MT debrided most of the necrotic wounds within one week, which was more rapid than all other non-surgical methods. Wound healing was more rapid during MT than during antecedent conventional therapy (p = 0.01). No complications were seen. We have demonstrated that MT can be beneficial in the treatment of pressure ulcers in persons with spinal cord injuries. MT was significantly more effective and efficient than the current, conventional treatment alternatives being used. MT was also safe, simple and inexpensive. MT can be a valuable modality in the treatment of pressure ulcers.

The circadian blood pressure pattern in ambulatory normal subjects

Ambulatory blood pressure (BP) monitoring using a portable noninvasive device capable of automatically measuring and recording BP every 7.5 minutes during a 24-hour study period was performed in 34 normal volunteers on 2 separate occasions, 2 to 8 weeks apart, to test the consistency of the whole-day blood pressure pattern. The average of all systolic BPs measured during the second study day was within 10 mm Hg of that measured during the first study day in 79% of the subjects, and the respective diastolic BP averages were within 5 mm Hg of each other in 65% of the subjects; 53% satisfied both of these criteria. The reproducibility of the circadian pattern of the BP was tested by dividing the 24-hour day into 12 consecutive 2-hour BP averages. When the corresponding 2-hour periods on the 2 study days were matched, there were strong correlations (r greater than 0.70) within most subjects for both the systolic and diastolic BP averages of the 2-hour periods (76% and 68% of subjects) and for the relative rank values of the periods (62% and 56%). Moreover, there were no significant differences between the averages (for all subjects together) on the 2 study days of the highest and lowest systolic and diastolic 2-hour BP values; similarly, the times at which these extreme values occurred on the 2 study days corresponded closely. Thus, in normal subjects there is a strong tendency for the circadian pattern and the actual levels of BP to be consistent between 24-hour study periods.

Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study.

It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment.

Helicobacter pylori Culture Supernatant Inhibits Binding and Proliferative Response of Human Gastric Cells to Epidermal Growth Factor: Implications for H. pylori Interference with Ulcer Healing?

Helicobacter pylori (H. pylori) infection of gastric mucosa is strongly associated with gastritis and peptic ulcer disease. However, the mechanisms of the ulcerogenic action of H. pylori and/or the interference of H. pylori with ulcer healing are unknown. Through binding to its receptor, epidermal growth factor (EGF) accelerates cells migration and triggers epithelial cell proliferation which are both important for the healing of gastroduodenal ulcers. H. pylori seems to interfere with ulcer healing, but the cellular and molecular targets and mechanisms of these actions have not been elucidated. In the present study, we tested the effect of H. pylori culture supernatant (dialyzed to remove molecules smaller than 10 kD) on EGF binding to its receptor and on the proliferative response of human gastric Kato III cells to EGF. H. pylori culture supernatant significantly reduced specific binding of EGF to its receptor and reduced EGF-stimulated gastric cell proliferation. Since ulcer healing requires epithelial cell proliferation and cell migration (re-epithelialization), which are both triggered by EGF binding to its receptor, the alteration in these mechanisms by H. pylori product may be the basis of H. pylori-induced interference with ulcer healing.

Helicobacter pylori: current perspectives.

Within the past decade, there has been an explosion of investigative activity and publications about Helicobacter pylori (H. pylori). Its role in gastroduodenal disease is becoming greater with definite etiologic association in chronic type B gastritis and a probable role in duodenal ulcer, a probable role in gastric ulcer, and possibly a factor in the development of interstitial type gastric carcinoma. Epidemiologic studies have shown H. pylori to be worldwide in distribution with higher prevalence rates and earlier initial infection rates in developing countries compared with industrialized nations. Person-to-person transmission appears to occur via the fecal–oral route. Pathogenesis of H. pylori-associated diseases remains unclear. We are, however, gaining insights into the role that H. pylori extracellular products play in damage to mucin and gastric epithelial cells as well as other gastroduodenal physiologic processes. Antimicrobial treatment, when effective, produces remission of mucosal pathologic changes and reduces duodenal recurrence rates. A major as yet unsolved problem is that there is no completely effective treatment regimen that consistently eradicates H. pylori in infected patients. Concepts of pathogenesis and future directions of research are discussed.

Effect of lithium carbonate on zidovudine-associated neutropenia in the acquired immunodeficiency syndrome

The acquired immunodeficiency syndrome (AIDS) is caused by infection with the human immunodeficiency virus (HIV). This condition causes a profound depression of cellular immunity, rendering the patient susceptible to certain infections. Currently, the only licensed agent shown to be effective in prolonging life in symptomatic patients infected with HIV is zidovudine (azidothymidine, AZT, 3’-azido-3’-deoxythymidine) [l]. Zidovudine is, however, associated with significant side effects. Myelosuppression appears to be the major side effect, and neutropenia, anemia, or thrombocytopenia often requires discontinuation of zidovudine therapy [2,3]. To date, the minimal effective dose of zidovudine has not been determined, although dosage reduction may be necessary when drug toxicity occurs. Lithium carbonate has been shown to cause sustained leukocytosis and neutrophilia in hematologitally normal patients with psychiatric disease [4-71. When given to patients receiving myelosuppressive therapy, lithium partially reverses neutropenia and thrombocytopenia [8,9]. In addition, lithium may help reduce infection and leukopenia during systemic chemotherapy [lo]. We report the effects of lithium on neutropenia associated with zidovudine therapy in five patients with AIDS.

Campylobacter pylori Interactions with Gastric Cell Tissue Culture

Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. tejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells.

Helicobacter pylori Induces Apoptosis in Human Epithelial Gastric Cells by Stress Activated Protein Kinase Pathway

The pathway by which Helicobacter pylori induces apoptosis in gastric epithelial cells is not known. The aim of this study was to determine whether H. pylori‐induced apoptosis is associated with SAPK/JNK activity in human gastric cancer KATO III cells.