Elevated Diastolic,But Not Systolic,Blood Pressure Measured in the Emergency Department Predicts Future Development of Hypertension in Normotensive Individuals

Elevated blood pressure (BP) is reported in many individuals without hypertension presenting to the emergency department (ED). Whether this condition represents a transient state or is predictive for the development of future hypertension is unknown. This observational prospective study investigated patients admitted to an ED without a diagnosis of hypertension in whom BP values were ≥140/90 mm Hg. The primary outcome was development of hypertension during follow‐up. Overall, 195 patients were recruited and at the end of follow‐up (average 30.14±15.96 months), 142 patients were diagnosed with hypertension (73%). The mean age (50±12.25 vs 48.31±13.9, P=.419) and sex distribution (78 men/64 women vs 24 men/20 women, respectively; P=.148) were similar in both groups. There were significant differences in systolic and diastolic BP between those who developed hypertension on follow‐up and those who did not (177.6 mm Hg±22.6/106.1 mm Hg±16.9 vs 168.6 mm Hg±18/95.2 mm Hg±12.2; P=.011 for systolic BP, P<.001 for diastolic BP). In multivariate analysis the only significant predictive factor for the development of hypertension was diastolic hypertension recorded in the ED (P=.03). Elevated diastolic, but not systolic, BP among patients presenting to the ED is associated with future development of hypertension in previously normotensive individuals.     

Trypsin liberates an arginine vasopressin-like peptide and neurophysin from a Mr 20,000 putative common precursor.

Although the hypothesis that vasopressin and its associated neurophysin are synthesized together in one macromolecular common precursor was put forward more than a decade ago, direct conformation of this hypothesis has been lacking. A [35S]cysteine-labeled putative precursor for vasopressin-related neurophysin (Mr 20,000, pI 6.1) has been isolated from the supraoptic nuclei of rats. This precursor was subjected to limited proteolysis with trypsin which produced a Mr 10,000 protein and peptide products. The former was identified as neurophysin on the basis of its pH-dependent affinity for vasopressin and its behavior in isoelectric focusing systems (pI 4.6-4.8). The tryptic peptides proved to be vasopressin-like because they: (i) were rich in cysteine, (ii) comigrated with vasopressin on gel filtration columns in 6 M guanidine HCl, (iii) bound to a neurophysin-Sepharose affinity column at pH 5.7, and (iv) were recognized by antibodies against vasopressin. These data on the Mr 20,000, pI 6.1 protein represent direct experimental evidence for a candidate for the common precursor of vasopressin and neurophysin. We propose that this common precursor be called "propressophysin."     

Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients

Preemptive ganciclovir therapy has reduced the occurrence of early cytomegalovirus (CMV) disease after hematopoietic stem cell (HSC) transplantation. However, late disease is increasingly reported. We describe 2 patients who developed late CMV central nervous system (CNS) disease after haploidentical HSC transplantation. Direct genotypic analysis was used to examine the presence of ganciclovir resistance. One patient had a mixed viral population in the cerebrospinal fluid (CSF), with coexistent wild-type and mutant UL97 sequences. The presence of 2 different strains was confirmed by subclone sequencing of the UL54 gene. One of the strains was different from the concurrent blood strain. The second patient had resistant variant in the lungs. These cases raise concern about the changing natural history of CMV disease in HSC transplantation, with emergence of previously uncommon manifestations following prolonged prophylaxis. Under these circumstances the CNS may be a sanctuary site, where viral persistence and antiviral drug resistance could result from limited drug penetration.     

Placebo-controlled trial to evaluate zidovudine in treatment of human immunodeficiency virus infection in asymptomatic patients with hemophilia. NHF-ACTG 036 Study Group.

One hundred ninety-three asymptomatic patients with hereditary coagulation disorders and human immunodeficiency virus (HIV) infection were studied in a controlled trial of zidovudine (ZDV) versus a placebo (with an average of 9.7 months on study). Pretreatment characteristics were well balanced between the placebo and drug-treated groups, including CD4 distributions, types of clotting disorders, transaminase abnormalities, and use of various hemostatic agents. At the time of analysis, 161 patients either were still receiving treatment or had previously reached an endpoint of disease progression while receiving treatment. Twenty-five patients withdrew voluntarily. The toxic effects noted included granulocytopenia and anemia, especially in older patients, and subjective symptoms of asthenia, malaise, and nausea, consistent with the known consequences of treatment with 300 mg ZDV five times daily. There was a trend toward more diagnoses of acquired immunodeficiency syndrome (AIDS), advanced or early AIDS-related complex (ARC), single ARC symptoms, or death in placebo recipients as compared with those receiving ZDV (22 v 13). Because older patients with hemophilia have more rapid disease progression, the same efficacy analysis was performed in the 89 patients aged more than 30 years who were receiving treatment. In this subgroup, there was a similar trend (11 v 6). With regard to the most advanced problems of the infection among the older patients, there were five patients who were newly diagnosed with AIDS or died in the placebo group versus none in the ZDV group (P = .02) among the older patients. The pretreatment distribution of CD4 counts for the placebo and ZDV groups were similar, but patients aged more than 30 years had significantly (P less than .049) fewer CD4 cells than patients aged less than 30 years. A beneficial ZDV effect is also supported by a trend toward higher CD4 counts (a 48-cell increase in the ZDV group at 24 weeks as compared with a four-cell increase in the placebo group) and a significant (P = .03) difference in weight gain in the ZDV patients aged more than 30 years (8 pounds) as compared with the older placebo patients (aged more than 30 years) (2 pounds) at week 24. The findings in the asymptomatic hemophilic patients aged more than 30 years support a useful effect of ZDV, which is similar to observations in the larger study of its use in asymptomatic, nonhemophilic patients.     

Schnyder's crystalline corneal dystrophy in association with hyperlipoproteinemia: histopathological and ultrastructural findings

A 61-year-old man with Schnyder's crystalline corneal dystrophy showed a slight reduction in vision during 16 years of observation. Plasma lipoprotein analysis done 10 years after presentation showed type IIA hyperlipoproteinemia, which was also detected in one of four siblings examined, none of whom showed the characteristic corneal dystrophy. Electron microscopic studies on corneal biopsy specimens from the patient showed abundant crystalline material and vacuoles predominantly in the superficial corneal stroma, with occasional keratocytes and rare basal epithelial cells containing laminated structures. The findings of a focal continuity between the trilaminar membrane around some of the stromal vacuoles and the plasmalemma of the keratocytes as well as dissolution of the plasmalemma in other keratocytes are consistent with the hypothesis of a local cellular role in the development of this corneal disorder.     

Fibrofolliculoma: solitary and multiple types

Multiple skin tumors generally show autosomal dominant inheritance and are sometimes associated with other cutaneous and internal lesions. Solitary growths are typically nonhereditary and unassociated with other abnormalities. We found only two previous reports of solitary fibrofolliculoma and only one of multiple fibrofolliculomas without associated lesions; a few publications describe multiple fibrofolliculomas in patients with perifollicular fibromas, trichodiscomas, acrochordons, and connective tissue nevus. We studied five new cases of solitary nonhereditary fibrofolliculomas and one of multiple familial fibrofolliculomas without associated lesions. Clinically, fibrofolliculomas were typically small growths with a central dilated follicle containing horny material. Histologically, there was characteristically a hyperplastic follicular infundibulum with a central keratinous plug, and anastomosing strands of basaloid cells branching into an angiofibromatous stroma. Fibrofolliculoma is thus another skin tumor in which patients with multiple growths showing autosomal dominant inheritance sometimes have associated abnormalities, while solitary lesions with identical clinical and microscopic features are relatively trivial and nonhereditary.     

Hemophiliac patient's knowledge and educational needs concerning acquired immunodeficiency syndrome

The Patient Knowledge Assessment Study (PKAS) was conducted among 107 male hemophilic patients, aged 15 to 67 years, at 19 hemophilia treatment centers (HTC). Participants were given a 30-item questionnaire concerning the cause of acquired immunodeficiency syndrome (AIDS), the groups at risk, and modes of transmission. The questionnaire included questions on the participant's status in regard to antibody to human T-lymphotropic retrovirus, type III/lymphadenopathy-associated virus (HTLV-III/LAV), and the meaning of this test result. HTC health-care providers were asked to complete a separate questionnaire containing 17 questions about information given patients concerning their HTLV-III/LAV antibody status and its meaning. Overall, patients had a good base of knowledge about AIDS; however, there were gaps in this knowledge. Twenty-nine percent of patients did not know that spouses of AIDS patients were at risk for AIDS; 47% did not know that sexual partners of persons with hemophilia were at risk; and 32% did not know that hemophilic children were at risk. Further, only 69% understood that antibody-positive individuals had had contact with the AIDS virus. Identifying these and other areas of misunderstanding will provide the information needed to design educational strategies and psychosocial support programs appropriate for the hemophilic population, and which may serve as a model for other populations.     

Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Introduction: Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood. Methods: We assessed liver damage and hepatocyte 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune‐deficient mice. Hepatic lymphocyte subpopulations were characterized. Lipopolysaccharide (LPS) treatment and bowel decontamination determined the role of gut antigens. Results: Discrete, round necrotic lesions were observed as early as 2 h following 70%, but not 30% PH. In immune competent mice the extent of hepatocyte necrosis inversely correlated with BrdU incorporation. T, natural killer and natural killer T cells were recruited to the liver early after PH; however, only T‐cell depletion abrogated hepatic necrosis. Hepatic injury was significantly reduced in non‐obese diabetic/severe combined immunodeficient mice undergoing PH, while BrdU incorporation was not affected. Liver injury was augmented by LPS injection and reduced by gut decontamination. Conclusions: A distinct pattern of early focal hepatic necrosis is observed following extensive PH in mice. T cells infiltrating the liver immediately after PH and gut‐derived antigens are indispensable for the observed liver necrosis and may thus provide therapeutic targets to ameliorate liver damage following PH.     

Multiple Forms of Arylalkylamine N-Acetyltransferases in the Rat Pineal Gland: Purification of One Molecular Form

Rat pineal serotonin N-acetyltransferase (EC 2.3.1.87) activity is isolated in two molecular forms (Mr approximately equal to 10,000 and 95,000) by high performance size exclusion liquid chromatography in the presence of ammonium acetate (0.1 M, pH 6.5). In the presence of sodium citrate (0.1 M, pH 6.5), however, it is eluted as a single peak of intermediate size (Mr approximately equal to 30,000). A highly enriched preparation of one of the molecular forms has been obtained by a two-step purification procedure involving disulfide-exchange and anion-exchange chromatography. The N-acetyltransferase in 250 pineal glands obtained from isoproterenol-treated rats can be purified about 80-fold in 1 day; recovery is about 3%. Polyacrylamide gel electrophoresis of the final preparation indicates that a single major band (Mr approximately equal to 11,000) is present; this appears to be serotonin N-acetyltransferase.