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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 19 recordsLinked to original sources

Crystallization and preliminary X-ray analysis of human endothelin.

Endothelin, a potent regulator of vasoconstriction and hypertension, is a naturally produced peptide of 21 amino acids containing two disulfide bonds. We have crystallized endothelin from humans using the vapor-diffusion technique, characterized the crystals by X-ray diffraction analysis, and have collected the X-ray intensities to a resolution of 1.8 A. The crystals, which demonstrate physical properties similar to most protein crystals and have a comparable solvent content, are hexagonal prisms that frequently grow to lengths of 400 microns and widths of 150 microns. The space group of the crystals is P6(1)22 (or P6(5)22), with a = 27.4, c = 79.6 A. There is one molecule of endothelin in the asymmetric unit of the crystals.

Crystallization

A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract.

BACKGROUND: Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival. METHODS: We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization. RESULTS: A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group. CONCLUSIONS: Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care.

Administration, Topical

Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: a clinical and pathological study.

The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.

Acquired Immunodeficiency Syndrome

Continuous positive airway pressure by face mask or mechanical ventilation in patients with human immunodeficiency virus infection and severe Pneumocystis carinii pneumonia.

We reviewed the records of 44 patients with AIDS who had 45 episodes of severe Pneumocystis carinii pneumonia (PCP). While 9 patients required intubation and mechanical ventilation (MV) on admission, continuous positive airway pressure (CPAP) by face mask was the initial measure in 36 episodes. There were 25 patients managed with CPAP alone, 23 of whom survived. Among the reasons for delayed intubation and MV (11 patients) was that treatment failure was strongly associated with non-survival, since all 6 such patients died. The in-hospital mortality for severe PCP in this study was 33% overall, and reached 65% for mechanically ventilated patients. The 1-year survival was 43% (95% confidence interval, 28%-58%). These data confirm the improved prognosis for patients with AIDS and severe PCP, and suggest that mask CPAP may be an adequate mean of ventilatory support in this setting.

Adult

Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys.

The blood level of erythropoietin (Epo) is often anomalously low in anemic patients with inflammatory or malignant diseases. Therefore, we studied effects of pure recombinant immunomodulatory peptides on Epo formation in cultures of the human hepatoma cell line, HepG2. Interleukin (IL)-1 beta, IL-1 alpha, and tumor necrosis factor alpha lowered Epo production with half-maximal inhibition at 2, 5, and 20 U/ml, respectively. IL-6, transforming growth factor beta 2 and interferon gamma did not inhibit. Furthermore, IL-1 beta (10 U/ml) proved to block Epo formation in isolated serum-free perfused rat kidneys. Proposedly, monokines play a role in the pathogenesis of Epo deficiency in various diseases.

Animals

Pain relief using cutaneous modalities, positioning, and movement.

Positioning, movement, and certain cutaneous modalities may be easily used by all caregivers, including the family, to bring comfort and pain relief to terminally ill patients with pain. For such patients, these techniques are most appropriately used in addition to pharmacologic control of pain. Patients themselves may use some of the cutaneous modalities with minimal assistance from others, thereby promoting a sense of independence. Other techniques may be performed by family and friends, providing them with the assurance that they are assisting a loved one. The techniques presented here can be readily used in the home or hospital setting and are relatively low risk, simple, and inexpensive. This paper presents specific guidelines for patients and caregivers in relation to the use of superficial massage, superficial heat and cold, menthol application to skin, transcutaneous electrical nerve stimulation (TENS), positioning, and movement. Because of their simplicity and ease of use, these techniques tend to be overlooked. However, taking the time to introduce these techniques to patients and families often results in a significant contribution to the comfort of the dying patient.

Cryotherapy

Evaluation of bacterial polysaccharide immune globulin for the treatment or prevention of Haemophilus influenzae type b and pneumococcal disease.

A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines. At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Hib by greater than 0.15 microgram/ml within 4-6 h and by 2-4 micrograms/ml at 72 h. Thereafter, antibody declined, with a mean half-life of 27 days. BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus-pertussis or Hib oligosaccharide-diptheria CRM197 conjugate vaccines. In high-risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Hib infection during infancy. Thus, BPIG may have utility in the prevention of Hib infections in high-risk patients who cannot be immunized adequately with Hib conjugate vaccines.

Antibodies, Bacterial

Prevention of Haemophilus influenzae type b infections in Apache and Navajo children.

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Antibodies, Bacterial

Diffusion of cefpirome into the cerebrospinal fluid of patients with purulent meningitis.

We evaluated the diffusion of cefpirome into the cerebrospinal fluid (CSF) of 25 patients with bacterial meningitis or ventriculitis who were receiving conventional antibiotic treatment. A single cefpirome dose of 2 g was infused at day 2-3 after the onset of therapy. Concentrations of cefpirome in serum and CSF obtained at 2, 4, 8 or 12 h after the infusion were determined by high-performance liquid chromatography. The mean (+/- S.E.M.) concentrations of cefpirome in CSF ranged from 2.26 +/- 1.16 to 4.17 +/- 0.83 mg/L. These concentrations were higher than the MBCs for the pathogens usually responsible for bacterial meningitis.

Adolescent

Maternal toxemia is associated with reduced incidence of germinal matrix hemorrhage in premature babies.

To evaluate prenatal and perinatal risk factors for development of germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), we conducted a prospective epidemiologic study of 449 babies whose birth weight was less than 1501 grams. This study permitted us to test our previously generated hypothesis that babies born to mothers with preeclampsia were at substantially reduced risk of developing GMH-IVH. Seventy-two (16%) of the babies in this population developed GMH-IVH. One (2.5%) of the 40 mothers with a diagnosis of preeclampsia and 71 (17.4%) of 409 mothers without preeclampsia gave birth to babies who developed GMH-IVH. GMH-IVH was seen in 6/107 (5.6%) of babies born to women with hypertension including 4/69 (5.8%) of babies born to women with pregnancy-induced hypertension, compared to 66/352 (18.8%) of babies born to mothers who did not have hypertension. Only 7.3% (8/108) of babies born to women who had proteinuria had GMH-IVH, compared to 18.3% (64/350) of babies whose mothers did not have proteinuria. GMH-IVH was seen in 5/89 (5.6%) of babies whose mothers had both hypertension and proteinuria, whereas 63/332 (19%) of babies born to mothers who lacked both factors, developed GMH-IVH. In stepwise logistic regression analysis, these significant findings were not explained by the presence of labor, postnatal acidemia, need for intubation, antenatal administration of steroids, birth weight, or gestational age. In addition, we found that maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Hemorrhage

Serum carcinoembryonic antigen: a prognostic marker in HIV-related Pneumocystis carinii pneumonia.

Serum concentrations of carcinoembryonic antigen (CEA) were measured in 43 consecutive patients with HIV-related Pneumocystis carinii pneumonia (PCP). The subjects were divided into 2 groups according to the severity of the PCP:PaO2 in ambient air (AA) less than or equal to 50 mmHg on admission (n = 22, group 1) and PaO2 greater than 50 mmHg (n = 21, group 2). In addition, 57 HIV patients with either non-PCP pulmonary diseases (n = 34, group 3) or extrapulmonary disease (n = 23, group 4) were studied. Mean CEA levels (ng/ml) were 13 +/- 10 in group 1 and 4.9 +/- 5.5 in group 2 (p less than 0.001). The corresponding values in groups 3 and 4 were much lower (2.7 +/- 1.8 and 2.4 +/- 1.8, respectively). In group 1, mean initial CEA levels were higher (p less than 0.001) in the patients who died (n = 6; 23.5 +/- 11) than in the survivors (n = 16; 8.9 +/- 7), although the initial mean PaO2 were identical (39 +/- 7 and 39 +/- 8 mmHg, respectively) and the initial mean LDH levels were not significantly different (1544 +/- 530 and 1200 +/- 457 IU/l). CEA levels fell during specific anti-PCP therapy associated with corticosteroids but returned to normal only in the survivors. We conclude that CEA levels are increased in patients with PCP and acute respiratory distress. Among the patients with PaO2 levels of less than or equal to 50 mmHg before treatment, only high levels of CEA (greater than 20 ng/ml) were associated with a fatal outcome, regardless of anti-PCP therapy associated with corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Accidental exposure to health care workers of blood and body fluids from patients].

Due to the growing concern of Health Care Workers (HCW) regarding the possibility of acquiring blood borne infections through accidental occupational exposure and the fact that HIV and Hepatitis B infections have occurred in that setting, an evaluation of the frequency of accidents and their circumstances, suffered by HCW with blood or body fluids from patients was carried out. 1,340 self administered questionnaires were given to HCW with direct contact with patients in a general 800 beds hospital, requiring information of accidental percutaneous, mucosal or cutaneous (it not intact) exposures to blood or certain (risky) body fluids ever and/or in the last 6 months. Sixty five percent of HCW referred some exposure ever and 46% in the last 6 months. The rate of exposure ever ranged from 36.6% in medical students to 69.5% in doctors, 78.5% in nurses to 100% in dentists. Seventy seven percent of the exposures were seen during routine care, 28.5% were perceived as due to personal carelessness, 19.9% due to patient agitation, 33.5% as inherent to the procedure and 8.9% to abandonment of material. Exposures were mostly to blood. One hundred eleven out of 331 (33.5%) exposures were produced during handling of syringes; 33.2% during invasive procedures and 13% during cleaning of material. Sixty out of 107 (56%) non surgical doctors (NSD) and 61/67 (92.5%) of surgical doctors (SD) had had exposures ever (p < 0.01), 16.8% and 65.6% had had one or more in the last 6 months respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational

Behavioural and developmental aspects of primary generalized myoclonic-astatic epilepsy.

The evolution of psychomotor development and behaviour was studied in 15 children with primary generalized myoclonic-astatic epilepsy and with developmental status adequate for age at final examination at school age following a mean follow-up period of 8.5 years. Temporary arrest of mental and motor development in 4 children was related to high seizure frequency or, in 3, to non-convulsive status. Different types of behavioural abnormalities were documented frequently during the course of the disorder; they were significantly related to active seizure periods and to a lesser extent to anticonvulsant medication. Persistent behavioural abnormalities were noted in 5 children. Hyperkinesia, short attention span and emotional lability were the most frequent complaints. None of the children needed special care and those followed-up until school age were seizure-free, without medication and in classes appropriate for their age. At initial examination the high probability of a favourable prognosis may be anticipated in children with normal development before seizure onset, lack of gross brain pathology and with strong indications (family history and/or EEG criteria) for a genetic predisposition. Nevertheless, repeated systematic re-evaluation for early recognition of possible developmental and/or behavioural deviances throughout the course of illness are recommended.

Child Behavior Disorders

High incidence rates of invasive pneumococcal disease in the White Mountain Apache population.

OBJECTIVE: In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. DESIGN: Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. SETTING: The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. PATIENTS: Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. OUTCOME MEASURES: The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. RESULTS: One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years--2396 per 100,000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. CONCLUSION: The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population.

Adolescent

[Outcome of prognostic factors of infectious endocarditis over a 16 year period. Apropos of 471 cases].

Four hundred and seventy one cases of infective endocarditis (IE) were reviewed: 338 native valve IE and 133 prosthetic valve IE (42 early and 91 late IE). Two periods were compared: 1973-1980 (250 cases) and 1981-1988 (221 cases). There was a decrease in native valve IE (78% to 64%) and an increase in late prosthetic valve IE (13% to 27%), little change with respect to age, causal cardiac disease, delay in diagnosis (except in native valve IE, 39 to 29 days), or frequency of complications, especially cardiac (50% and 51%). However, global mortality decreased from 41% to 27% (p < 0.001). The evolution of the frequency of cardiac complications, cardiac surgery and mortality for the two periods was: for native valve IE respectively 53% to 42%, 41% to 37%, 37% to 20% (p < 0.005); for early prosthetic valve IE respectively, 45% to 55%, 41% to 55%, and 82% to 50% (p < 0.05); for late prosthetic IE, respectively 34% to 69%, 34% to 69% and 37% to 36%. The frequency of surgery had therefore little influence on prognosis except in early prosthetic valve IE. The percentage of infections which could not be controlled medically decreased from 17% to 11%. The mortality of unoperated patients decreased from 46% to 28% (p < 0.01), suggesting more effective antibiotherapy, and the mortality of operated patients fell from 34% to 26%. Global surgical mortality was 35% in the acute phase (positive valve culture), 14% after sterilisation (p < 0.001) and the corresponding frequencies of paravalvular leaks was 17% and 4% (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Immunologic studies in patients with dilated cardiomyopathy].

In 10 cases of dilated cardiomyopathy the HLA-loci (A, B, C, DR) and marker expression on lymphocytes were studied. In this group the T4/T8-ratio was decreased and interleukin-2-expression was increased in relation to normals or patients with chronic coronary heart disease, respectively. 9 patients had the HLA-A1 or HLA-A2-locus in their siblings. In correlation analysis between immunological and hemodynamic parameters a good correlation of the number of NK-cells to the ejection fraction (r = 0.79) and negative correlation of helpercells (CD4) to the cardiac output were found (r = -0.80). The results of this attempt suggest an immunological pathogenesis of the dilated cardiomyopathy.

Adult