Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.

OBJECTIVE: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease. METHODS: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. RESULTS: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. CONCLUSION: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

Reciprocal interactions between human cytomegalovirus and human T cell leukemia-lymphoma virus type I in monocyte-derived macrophages cultured in vitro.

Infection of macrophages with human cytomegalovirus (HCMV) has been shown to be nonlytic and exclusively cell associated. Human T cell leukemia-lymphoma virus type I (HTLV-I) is capable of establishing productive infection in macrophages. We studied the interactions between HCMV and HTLV-I in monocyte-derived macrophages cultured in vitro. We found that coinfection of macrophages with HCMV and HTLV-I significantly enhanced HCMV replication, resulting in release of infectious HCMV from dually infected cells. On the other hand, HCMV inhibited HTLV-I replication in macrophages coinfected with both viruses. Reciprocal interactions between HCMV and HTLV-I were mediated by their trans-acting proteins. Results of transfection studies demonstrated that the tax gene product of HTLV-I alone was capable of upregulating HCMV production. In a transient gene expression assay the immediate-early 2 (IE2) protein of HCMV alone could inhibit HTLV-I replication, whereas the IE1 protein, which had no effect by itself, produced a synergistic inhibitory effect together with the IE2 protein. Results from this study suggest that in vivo double infection of macrophages with HCMV and HTLV-I may contribute to the dissemination of HCMV infection in patients suffering from HTLV-I-associated T cell leukemia-lymphoma.

Use of nipple stimulation to obtain contraction stress test.

A total of 1312 nonstress tests were performed in the 14-month period between May 1, 1981, and June 30, 1982. There were 323 tests in 194 patients that were nonreactive and subsequently required a contraction stress test using nipple stimulation. The authors found that the results obtained using nipple stimulation were as predictable as contraction stress tests using oxytocin infusion.

Wrongful birth, wrongful life: the doctor between a rock and a hard place.

Recent court decisions and advances in medical technology have put the doctor in the position of serving many masters at the same time. The conflicts created often do not deal with good or bad medicine, but rather with the concept of alternative choices. It is unfair to ask the medical field to be solely responsible for making decisions involving such widespread social and economic consequences.

Effects of TRH on gastric acid secretion: a model for human study.

The possible effects of TRH administration on different parameters of gastric function were studied in 10 patients with different gastrointestinal complaints. Basal (BAO) and pentagastrin stimulated (6 micrograms pentagastrin/kg bw sc) maximal (MAO) acid output were determined and serum levels of TSH, total and free thyroxine (T4 and FT4), triiodothyronine (T3) were measured. After determinations of BAO and MAO and the hormones indicated above, one group of patients received a TRH injection (0.2 mg protirelin) intravenously. The second group of patients was injected with atropine (atropinum sulfuricum, 1 mg, iv). At different times following the injections in both groups of patients BAO, MAO and serum levels of TSH, total and free T4, T3, gastrin were determined. Injection of TRH resulted in an increase in TSH and with some delay in thyroxine and gastric acid levels. Atropine treatment was followed by a decrease in gastric acid secretion and a small decrease in TSH and no changes in the values of the other studied hormones. The results suggest a complex interrelationship between TRH, vagal system and pentagastrin-dependent gastric acid secretion operating in human subjects.

Caries prevalence of preschool children in Baja, Hungary, in 1975 and 1982: effect of a supervised monthly NaF mouthrinsing program.

The aim of the study was 1) to compare the caries prevalence of preschoolchildren in Baja with data from 1975 and 2) to evaluate the effect of 0.2% sodium-fluoride mouthrinsings practiced during the last 4 yr. In 20 kindergartens of Baja 1462 children between 3 and 6 yr of age were investigated. All the children were participants in an oral hygiene motivation program and fluoride rinsings, performed generally monthly, but at least 10 times in a year. The dental investigations of the primary teeth were carried out by the same team as in 1975. The frequency of caries-free children increased from 18.8% in 1975 to 24.8% in 1982. The dmft mean values decreased only in the 5- and 6-yr-old children.

Caries prevalence of preschoolchildren in Baja, Hungary in 1955 and 1975.

In 1975 caries epidemiologic investigations were performed in 1,017 preschoolchildren of Baja, aged 3--6 years. The data were analyzed and compared with those of 620 preschoolchildren of the same city in 1955. A mean increase of 10.9% of the caries frequency (percentage of examinees with caries), and a mean increase of 43.5% of the caries intensity(dmft count per examinee) could be observed in spite of a better vitamin D prophylaxis. The possible cariogenic role of the increased surgar consumption (37.5 kg from 24.4 kg per individual during 20 years) is discussed.

Experience with a nurse practitioner program in the surgical department of a children's hospital.

Manpower limitations are occurring in residency programs because of fewer residency positions and increasing governmental regulations. This limitation prompted the development of a program to utilize pediatric nurse practitioners (PNPs) in our Department of Surgery. Two began in September 1989. Their role was similar to that of the junior resident and included collaborative management of patients, admission evaluations, discharges, and a variety of procedures. The impact of this program was evaluated by questionnaire to attending surgeons, house staff, and parents. There were 123 surveys mailed (12 attending surgeons, 46 residents, 65 parents). The overall response rate was 51% (100% attending surgeons, 57% residents, and 38% parents). Only two of the attending surgeons had previous experience working with a PNP. All attending surgeons were enthusiastic about the PNP role in managing their patients and felt the PNP had decreased the workload of the resident. Eighty-three percent did not feel the PNP interfered with resident learning; 17% were undecided. Eleven of 12 felt the PNP had helped communication between them and their patients; one was undecided. The resident responses were assessed by level of training. Among senior residents, 82% felt the PNP had decreased the workload of the junior resident and 91% viewed the PNP as a valuable resource, whereas 87% of the junior residents felt the PNP decreased their workload and 100% felt the PNP was a valuable resource. None of the residents felt the PNP interfered with their learning and 73% of the junior residents and 55% of the senior residents felt the PNP contributed to their learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of pancuronium bromide to inhibit fetal movement during magnetic resonance imaging. A case report.

Magnetic resonance imaging has been of limited value in fetal evaluation due to the prolonged duration of image construction and uncontrolled fetal movement. This limitation can be overcome safely by immobilizing the fetus with an intramuscular injection of pancuronium bromide.

Combined intravascular and intraperitoneal transfusions for erythroblastosis fetalis. A report of two cases.

In two cases of erythroblastosis fetalis, combined intravascular and intraperitoneal transfusions were used successfully.

Elevated maternal serum alpha-fetoprotein values. How low is high?

Most maternal serum alpha-fetoprotein (MSAFP) screening programs are set up with the goal of prenatal detection of fetal neural tube defects. It is also commonly accepted that MSAFP testing yields many false-positive results. Screening programs commonly utilize schemata that identify abnormal levels of MSAFP as greater than 2.5 multiples of the median (MOM) and also recommend two abnormal values before initiating ultrasound evaluation. Our pilot program evaluating obstetric outcomes found that 21 of the 29 women with elevated MSAFP values (greater than 2.0 MOM) eventually developed significant pregnancy management changes or complications of pregnancy. Thus, we believe that the use of MSAFP screening solely for the purpose of detecting fetal neural tube defects is inconsequential relative to its usefulness in detecting other pregnancy abnormalities. We also believe that ultrasound evaluation should be accomplished after the first abnormal value and that the cutoff of 2.5 MOM should be lowered to at least 2.0.

Effects of doxazosin on hemorheological, hemodynamic and lipid parameters in patients with essential hypertension.

It is known from previous studies that hemorheological parameters are altered in patients with essential hypertension. The hemorheological and hemodynamical effects of doxazosin, a selective alpha-1-adrenoreceptor blocker agent, was examined in twenty patients (mean age: 54+/-10 years) with essential hypertension. Hemorheologic (hematocrit, fibrinogen, plasma and whole blood viscosity) and hemodynamic (cardiac output and index, total peripheral resistance) parameters and plasma lipids were determined. The measurements were carried out before the beginning of the treatment, after 1 week and after 12 weeks treatment periods. Besides significant reduction of blood pressure and total peripheral resistance (p < 0.001), a decrease in cholesterol (p < 0.001) and triglyceride (p < 0.01) levels and a beneficial effect on hemorheological parameters was detected. Fibrinogen and plasma viscosity decreased significantly (p < 0.01). Hematocrit value was also lower after one week (p < 0.001), then an increase could be seen. Whole blood viscosity showed similar changes as hematocrit, but the degree of its final increase was slighter, which was supported by the significantly lower value of corrected blood viscosity (p < 0.05).

Hemorheological and hemodynamic parameters in patients with essential hypertension and their modification by alpha-1 inhibitor drug treatment.

Hemorheological factors play an important role in the pathogenesis of different cardiovascular diseases. The hemorheological and hemodynamic parameters in essential hypertension and their possible modification by antihypertensive treatment were examined in the following two studies. In the first study the fundus appearance and hemorheological parameters (plasma and whole blood viscosity (WBV), fibrinogen level) of 33 hypertensive patients (mean age: 55 years) were examined. The fundus appearance showed retinopathy in all the cases between stages I-III. All the measured hemorheological parameters of the examined patients were in the pathological range (WBV at 90 s(-1): 5.18 mPa s) and were significantly (p < 0.01) higher than in healthy controls (WBV at 90 s(-1): 4.18 mPa s). The hemorheological factors showed a parallel deterioration with the fundus appearance, namely their values were significantly (p < 0.01) higher in patients with a fundus appearance stage III (WBV at 90 s(-1): 6.02 mPa s) than stage I (WBV at 90 s(-1): 4.51 mPa s). These results show that there is a correlation between hemorheological parameters and fundus appearance in hypertensives, and this suggests that hemorheological factors may play a role in the development of hypertensive retinopathy. In the second study the hemorheological and hemodynamical effects of Doxazosin, a selective alpha-1-adrenoreceptor blocker agent, was examined in twenty patients (mean age: 54 years) with essential hypertension. Hemorheologic (hematocrit, fibrinogen, plasma and whole blood viscosity) and hemodynamic (cardiac output and index, total peripheral resistance) parameters and plasma lipids were determined. The measurements were carried out before the beginning of the treatment, after 1 week and after 12 weeks treatment periods. Besides significant reduction of blood pressure and total peripheral resistance (p < 0.001), a decrease in cholesterol (p < 0.001) and triglycerides (p < 0.01) levels and a beneficial effect on hemorheological parameters was detected. Fibrinogen and plasma viscosity decreased significantly (p < 0.01). Hematocrit value was also lower after one week (p < 0.001), then an increase could be seen. Whole blood viscosity showed similar changes as hematocrit, but the degree of its final increase was slighter, which was supported by the significantly lower value of corrected blood viscosity (p < 0.05). All these findings indicate that hemorheological factors may play a role in the pathogenesis and in the development of organ damages in hypertension.

Material changes in osteoporotic human cancellous bone following infiltration with acrylic bone cement for a vertebral cement augmentation.

Bone cement infiltration can be effective at mechanically augmenting osteoporotic vertebrae. While most published literature describes the gain in mechanical strength of augmented vertebrae, we report the first measurements of viscoelastic material changes of cancellous bone due to cement infiltration. We infiltrated cancellous core specimen harvested from osteoporotic cadaveric spines with acrylic bone cement. Bone specimen before and after cement infiltration were subjected to identical quasi-static and relaxation loading in confined and free compression. Testing data were fitted to a linear viscoelastic model of compressible material and the model parameters for cement, native cancellous bone, and cancellous bone infiltrated (composite) with cement were identified. The fitting demonstrated that the linear viscoelastic model presented in this paper accurately describes the mechanical behaviour of cement and bone, before and after infiltration. Although the composite specimen did not completely adopt the properties of bulk bone cement, the stiffening of cancellous bone due to cement infiltration is considerable. The composite was, for example, 8.5 times stiffer than native bone. The local stiffening of cancellous bone in patients may alter the load transfer of the augmented motion segment and may be the cause of subsequent fractures in the vertebrae adjacent to the ones infiltrated with cement. The material model and parameters in this paper, together with an adequate finite-element model, can be helpful to investigate the load shift, the mechanism for subsequent fractures, and filling patterns for ideal cement infiltration.

Solid tumors in children.

A thorough understanding of the incidence, clinical presentation, treatment, prognosis, and psychosocial issues surrounding children with solid tumors enables the nurse to actively participate on the health care team. Although significant advances over the past two-and-a-half decades to improve the outcomes of children with cancer have occurred, there remains room for continued improvement, especially among children with advanced-stage nephroblastoma, neuroblastoma, HCC, and teratoma.

Clinical study on the effect of amine fluoride/stannous fluoride on exposed root surfaces.

The aim of this study was to assess the remineralizing effect of an amine fluoride (AmF)- and stannous fluoride (SnF2)-containing toothpaste and mouthrinse on exposed root surfaces. A total of 44 adults participated in the 20-week, double-blind study and were grouped as follows: (1) 20 participants (mean age 45.7 years) used an AmF/SnF2 experimental toothpaste plus AmF/SnF2 (Meridol) mouthwash, and (2) 24 participants (mean age 48.8 years) used an NaF-containing toothpaste and mouthrinse. Root caries index (RCI) and root surface scores were determined by a modified method of Katz (J Dent Res, 1984). RCI mean values showed decreases of approximately 47% in the AmF/SnF2 group, and 10% in the NaF group. With respect to root caries scores, the number of persons with decreased softened (non-carious) surfaces between the baseline and control examinations was statistically significant (p less than 0.05) in the AmF/SnF2 group but not significant in the NaF group. A statistically significant difference (p less than 0.05) in the results of the groups favored the AmF/SnF2 subgroup. Thus, the data point to a possible remineralizing effect of topically applied AmF/SnF2 on softened root caries surfaces.

Nurse practitioners in acute care units.

The launch of the UKCC's The Scope of Professional Practice and measures to reduce junior doctors' working hours have once again raised debate on what roles are appropriate for nurses. For many, the development of the nurse practitioner role, with its advanced skills and increased levels of autonomy, offers a very desirable template. Much can be learned from the experience of US nurses, and this article describes a relatively recent innovation--the development of the nurse practitioner role in the acute hospital setting. The role is not a physician substitute; rather, it strengthens and promotes a multidisciplinary approach to patient care and presents the nurse with an opportunity to improve the delivery of care provided in the inpatient environment. Most significantly, it remains a nursing role.

[Experience with laparoscopic adrenalectomy in 25 cases]. / Laparoszkópos adrenalectomiával szerzett tapasztalataink 25 eset kapcsán.

Between July 1997, and April 1999 the authors performed 25 transperitoneal laparoscopic adrenalectomies. Conversion due to bleeding in 3 cases and due to unsuspected malignancy in 1 case was necessary. Complete resection was carried out in 22 cases. In 3 cases where a well circumscribed adenoma was visualized, only enucleation was performed. A new approach for left sided resection was also introduced. In the authors experience laparoscopy is an absolutely suitable intervention for the benign diseases of the adrenal glands. It assures a short, uncomplicated and painless postoperative period for the patients, with the same effectivity and safety compared to the conventional method.

[Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C]. / Oxidatív stressz és antioxidáns védelem alkoholos májbetegségben és krónikus C hepatitisben.

In the past decade it became accepted that free radicals, lipid peroxidation and antioxidant defense play a role in various tissues damages, thus in certain liver diseases as well. Since only limited data have been reported concerning the oxidative stress in viral hepatitis, a comparative study was performed in patients (pts) with chronic hepatitis C and alcoholic liver disease. In addition, the effects of a flavonolignan drug silymarin were assessed. 10 pts with chronic hepatitis C, 5 pts with alcoholic hepatitis and 13 pts with alcoholic cirrhosis have been investigated. Biochemical liver tests (serum bilirubin, aminotransferases, ALT, AST, lactate dehydrogenase (LDH), pseudocholinesterase, prothrombin), malandialdehyde (MDA) levels in plasma and red blood cell (RBC) hemolysate, superoxide radical generating capacity of stimulated polymorphonuclear granulocytes (PMN), plasma concentrations of reduced (GSH) and oxidized (GSSG) glutathione, vitamin A, luteine and beta carotene, furthermore RBC superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were determined. The level of plasma MDA--as the marker of lipid peroxidation--was highest in alcoholic cirrhosis (five times of normal) (p < 0.05), the RBC hemolysate MDA was most elevated in chronic hepatitis C (p < 0.05). The mean PMNs' superoxide radical generating capacity was 116.6% of normal control in alcoholic hepatitis, where the mean GSH level was the lowest (89.8% of normal). Plasma vitamin A content was lowest in alcoholic cirrhosis (68% of control) (p < 0.05). SOD activity was elevated in both chronic hepatitis C and alcoholic cirrhosis, where GPx activity was decreased (p < 0.05). There was a correlation between LDH and SOD activities (r = 0.77, p = 0.015). Silymarin treatment of one month duration resulted in normalization of serum bilirubin in 55% of treated pts, AST became normal in 45%, and RBC hemolyzate MDA level normalized in similar rate. A significant increase in both GSH and retinoids was found. Alterations in oxidative stress and antioxidant defense system were shown in chronic hepatitis C, not only in alcoholic liver disease. The parameters of lipid peroxidation and antioxidant defense may be useful surrogate markers for monitoring pts with liver disease during hepatoprotective treatment.

CFO spends two grueling weeks at Harvard.

Joseph A. Ruffolo spent two grueling weeks at Harvard Business School last June--the top award in the third annual Cain Brothers, Shattuck & Co. contest that recognizes an outstanding member of the healthcare financial community. Mr. Ruffolo, vice president of finance at Millard Fillmore Hospitals in Buffalo, N.Y., gives some advice to the next winner: Stock up on sleep before you go, and leave the tennis racket at home.