Post-traumatic epidural hematoma in two patients with long-standing “arrested” hydrocephalus

The occurrence of a post-traumatic epidural hematoma in two patients with long-standing arrested hydrocephalus is reported. There was a relatively long interval between the head injury and the onset of symptoms. The large hematoma was accommodated by the decrease in size of the markedly dilated ventricles. This report stresses the possibility of the presence of an epidural hematoma in the management of head injury in patients with long-standing arrested hydrocephalus.     

Phase I clinical and pharmacokinetic study ofN 4-behenoyl-1-β-d-arabinofuranosylcytosine

A phase I study ofN ⁴-behenoyl-1-β-d-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg^?1 which was escalated up to 7 mg kg^?1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg^?1. In Schedule 2, the daily dose was started with 1.5 mg kg^?1 which was escalated up to 8 mg kg^?1 and given for 2–16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg^?1 daily × 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg^?1 of BHAC were administered the half-lives of the initial phase (t _1/2α) and the second phase (t _1/2β) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin’s disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.     

Significance of Levocarnitine Treatment in Dialysis Patients

Carnitine is a naturally occurring amino acid derivative that is involved in the transport of long-chain fatty acids to the mitochondrial matrix. There, these substrates undergo β-oxidation, producing energy. The major sources of carnitine are dietary intake, although carnitine is also endogenously synthesized in the liver and kidney. However, in patients on dialysis, serum carnitine levels progressively fall due to restricted dietary intake and deprivation of endogenous synthesis in the kidney. Furthermore, serum-free carnitine is removed by hemodialysis treatment because the molecular weight of carnitine is small (161 Da) and its protein binding rates are very low. Therefore, the dialysis procedure is a major cause of carnitine deficiency in patients undergoing hemodialysis. This deficiency may contribute to several clinical disorders in such patients. Symptoms of dialysis-related carnitine deficiency include erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension. However, levocarnitine administration might replenish the free carnitine and help to increase carnitine levels in muscle. This article reviews the previous research into levocarnitine therapy in patients on maintenance dialysis for the treatment of renal anemia, cardiac dysfunction, dyslipidemia, and muscle and dialytic symptoms, and it examines the efficacy of the therapeutic approach and related issues.     

Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.     

Urinaryα 1 as an index of proximal tubular function in early infancy

Urinary ₁-microglobulin (U-A₁M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A₁M was high until day 14 and declined thereafter. It was significantly correlated with urinary ₂-microglobulin (U-B₂M) throughout the study, but not with serum A₁M on days 1 or 7. Similar to U-B₂M, U-A₁M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A₁M as well as U-B₂M was high on days 1–7 and then decreased to normal levels, suggesting that U-A₁M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A₁M is a useful index of proximal tubular function in early infancy.     

Colon-specific delivery of budesonide with azopolymer-coated pellets: therapeutic effects of budesonide with a novel dosage form against 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats.

The objective of this study was to achieve colon-specific delivery of budesonide using azopolymer-coated pellets and to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. After oral administration of azopolymer-coated pellets containing budesonide, a significant increase was observed in the therapeutic effects of the drug accompanied by a decrease in its systemic adverse effects when compared with oral administration in saline or rectal administration by enema. In addition, with the use of the colon-specific oral dosage form the dose of budesonide could be reduced. These results suggested that azopolymer-coated pellets may be a useful dosage form for the colon-specific delivery of budesonide as an anti-inflammatory steroid drug to bring about the healing of TNBS-induced colitis in rats.     

Purification and Partial Characterization of an Indomethacin Hydrolyzing Enzyme from Pig Liver

Purpose. Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. Methods. An indomethacin hydrolyzing enzyme was purified to homogeneity from pig liver microsomes using columns of Q-Sepharose, Red-Sepharose and Blue-Sepharose. The enzyme activity was assayed by measuring of -chlorobenzoic acid liberated from indomethacin by HPLC. Results. The purified enzyme effectively hydrolyzed the amide linkage in indomethacin but not those in -naphthylacetate and -nitrophenylacetate, which are typical substrates for carboxylesterase. The subunit molecular mass of the enzyme was 65 kDa according SDS-polyacrylamide gel electrophoresis. The Michaelis constant (Km) and maximum velocity (Vmax) values for indomethacin were 67.8 µM and 9.02 nmol/min/mg protein, respectively. The amino acid sequence analysis of the enzyme after cyanogen bromide cleavage showed high homology with a mouse carboxylesterase isozyme designated as ES-male. The activity of indomethacin hydrolysis was relatively high in the pig, rabbit and human liver homogenate, but not in those from rat and mouse. On the other hand, purified human liver carboxylesterases pl 5.3 and 4.5, and pig liver carboxylesterases have no catalytic activity for indomethacin. Conclusions. These results indicate that the hydrolysis of amide-linkage of indomethacin in humans would be associated with an enzyme similar to the indomethacin hydrolyzing enzyme from pig liver microsomes described here.     

Measurement of local blood flow of the intestine by hydrogen clearance method; Experimental study

Local blood flow of the bowel wall was measured by hydrogen clearance method both in the muscular and submucosal layers in the mongrel dog, separately and concurrently. A platinum wire electrode with a bare tip of 0.5 mm in length and 0.2 mm in diameter was inserted into each layer. About 10 per cent hydrogen gas was inhalated directly through the side hole attached to the endotracheal tube for 1–2 minutes and the obtained clearance curves were plotted on the semi-logarithmic scale, which was almost monoexponential. The results obtained were as follows:

1. Mean basal perfusion rate of the muscular layer of the intestine was 0.81–0.92 ml/min/gm, whereas that of the submucosal layer was 1.29–1.31 ml/min/gm, respectively. There was little difference of perfusion rates between the small and the large intestine. The results showed good correlationship with those reported by other authors.
2. The effect of vasoactive substances such as vasoconstrictor and vasodilator on the local blood flow in the bowel wall was confirmed.
3. This method is repeatedly applicable for measurement and also renders the information on the distribution of blood flow in the splanchnic area.

     

Esophageal pressure and apnea hypopnea index in sleep-disordered breathing

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in six cases of upper airway resistance syndrome (UARS) and 11 cases of obstructive sleep apnea syndrome (OSAS). The severity of negative Pes was represented by the highest peak (Pes Max) and the number of increased episodes (more than 13.5 cmH2O) per h (NPesI13.5). There was no significant correlation between Pes indices and AHI. Pes Max and NPesI13.5 were not different among severe OSAS (AHI > 30), mild OSAS (AHI < 30) and UARS. Apnea hypopnea index failed to represent the severity of negative Pes, which is an important aspect of the pathophysiology of sleep-disordered breathing.     

Joint proprioception in the elderly with and without hip fracture

OBJECTIVES: Decreased proprioception may contribute to the risk of falls in elderly patients. The purpose of this study is to determine whether patients with hip fractures have decreased hip proprioception compared with aged-matched controls, and whether hip proprioception differs in patients with repaired fractures compared with patients who have undergone prosthetic hip replacement after hip fracture. DESIGN: Retrospective. PATIENTS/PARTICIPANTS: Both hips of twenty-four hip fracture patients and age-matched patients without hip fractures were studied. Hip fracture patients were divided into osteosynthesis (twelve hips) and hemiarthroplasty (twelve hips) groups. INTERVENTION: Reproducibility of index angles (thirty hip flexion and thirty hip abduction) were compared with a six-degree-of-freedom electrogoniometer (instrumented spatial linkage; angular accuracy +/-0.5 degrees). RESULTS: There was no significant difference (flexion, p > 0.20; abduction, p > 0.67) in joint proprioception between fracture and no fracture groups. Likewise, there was no difference (flexion, p > 0.99, abduction; p > 0.74) in joint proprioception between osteosynthesis and hemiarthroplasty groups. CONCLUSIONS: Joint proprioception of hip fracture patients was not found to be diminished compared with age-matched normal controls. Additionally, replacement of the femoral head did not reduce joint proprioception compared with osteosynthesis with an intact femoral head. Maintenance of the femoral head does not seem to be necessary for the maintenance of joint proprioception in elderly hip fracture patients.