Sensory and motor deficits in children with cerebral palsy born preterm correlate with diffusion tensor imaging abnormalities in thalamocortical pathways

Aim  Cerebral palsy (CP) is frequently linked to white matter injury in children born preterm. Diffusion tensor imaging (DTI) is a powerful technique providing precise identification of white matter microstructure. We investigated the relationship between DTI-observed thalamocortical (posterior thalamic radiation) injury, motor (corticospinal tract) injury, and sensorimotor function.
Method  Twenty-eight children born preterm (16 males, 12 females; mean age 5y 10mo, SD 2y 6mo, range 16mo–13y; mean gestational age at birth 28wks, SD 2.7wks, range 23–34wks) were included in this case–control study. Twenty-one children had spastic diplegia, four had spastic quadriplegia, two had hemiplegia, and one had ataxic/hypotonic CP; 15 of the participants walked independently. Normative comparison data were obtained from 35 healthy age-matched children born at term (19 males, 16 females; mean age 5y 9mo, SD 4y 4mo, range 15mo–15y). Two-dimensional DTI color maps were created to evaluate 26 central white matter tracts, which were graded by a neuroradiologist masked to clinical status. Quantitative measures of touch, proprioception, strength (dynamometer), and spasticity (modified Ashworth scale) were obtained from a subset of participants.
Results  All 28 participants with CP had periventricular white-matter injury on magnetic resonance imaging. Using DTI color maps, there was more severe injury in the posterior thalamic radiation pathways than in the descending corticospinal tracts. Posterior thalamic radiation injury correlated with reduced contralateral touch threshold, proprioception, and motor severity, whereas corticospinal tract injury did not correlate with motor or sensory outcome measures.
Interpretation  These findings extend previous research demonstrating that CP in preterm children reflects disruption of thalamocortical connections as well as descending corticospinal pathways.     

TREATMENT OF PATIENTS WITH RETROGRADE EJACULATION IN THE ERA OF MODERN ASSISTED REPRODUCTION TECHNOLOGY

Purpose

We determined a rational strategy for treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology.

Materials and Methods

In 7 consecutive patients medical treatment or retrieval of spermatozoa from the bladder was performed at a male infertility clinic.

Results

Antegrade ejaculation was restored in 3 patients, and spermatozoa were retrieved from the bladder and used for assisted reproduction in 3. Spermatozoa with good oolemma penetrating ability were collected by seminal vesicle massage.

Conclusions

Modern assisted reproduction technology is a powerful treatment option for retrograde ejaculation when combined with a technique to retrieve spermatozoa of good quality from the bladder.     

Clinical sepsis in neonates is responsible for the lower prevalence of developing allergy

BACKGROUND: The hygiene hypothesis proposes an association between the change in exposure to microbes and the increased incidence of atopic disease. The purpose of the present study was to perform a prospective epidemiological study of the effect of perinatal infection on the development of allergy. METHODS: Eight hundred and ten children were born at Umeda Gynecological Hospital in Yamaguchi prefecture in Japan between April 1997 and March 1998. A questionnaire survey on the development of allergic diseases was sent by mail in 2002. The presence or absence of neonatal infectious disease (clinical sepsis) and maternal complications during the gestational period and delivery, and the incidence of bacterial infection during the perinatal period, were investigated by examining hospital records. RESULTS: Data were obtained for 410 children (51%). One hundred and forty-eight children (36.1%) developed allergic diseases. Among children whose mothers had allergies, the percentage of children who developed allergic disease(s) was significantly lower in children who had had clinical sepsis in the neonatal period than in those without clinical sepsis (26.1% vs 49.7%, P < 0.03). CONCLUSIONS: Clinical sepsis in neonates might reduce the risk of developing allergic diseases in early childhood in children whose mothers have allergies.     

Developmental changes in mucosubstances revealed by immunostaining with antimucus monoclonal antibodies and lectin staining in the epithelium lining the segment from gizzard to duodenum of the chick embryo

The mucosubstances in the epithelium lining the segment from gizzard to duodenum during development of the chick embryo was studied histochemically using monoclonal antibodies against gizzard mucus and lectins, with attention to the regional differentiation of the epithelium in this segment. The anterior limit of epithelial CdxA mRNA expression detected by in situ hybridisation, which served as the position of the gizzard-duodenal boundary, was clearly found from d 3. Granules positive for some antibodies or lectins were found in the region ranging from the posterior part of the gizzard to the duodenum at d 3, which was followed by an increase in the number of granules and a gradual enlargement of the granule-positive area to the anterior part of the gizzard over 4–6 d. From d 4, the epithelia of the gizzard body and of the pyloric or duodenal region came to be differently stained with some antibodies or lectins. From d 10, each region showed a specific pattern of staining. The epithelia of the gizzard body and pyloric region contained abundant mucus granules with a different staining pattern. In the duodenum the number of stained granules was low except in occasional goblet cells. Thus the epithelia of the gizzard body, pyloric region and duodenum may produce different mucosubstances and the regional differentiation in these epithelia may start at rather early stages soon after the formation of digestive tube.     

The neuronal and endothelium-dependent relaxing responses of human corpus cavernosum under physiological oxygen tension last longer than previously expected

BACKGROUND: Intracavernosal oxygen tension varies greatly in the process of erection. Blood extracted from the human penis demonstrates an increase from approximately 30 mmHg Po(2) in the flaccid state to 100 mmHg in the erect state of the penis. In the present study, using these levels as a guide, we investigate how the NO-dependent relaxation of human corpus cavernosum changed under physiological oxygen tensions ranging from approximately 30 to 100 mmHg. METHODS: Human penile tissue specimens were obtained at penile surgery with informed consent from the patients. The preparations were mounted in Krebs solution in an organ bath and the isometric tension was recorded. Krebs solutions of various oxygen tensions were prepared by bubbling 5% CO(2) in N(2) and O(2). The NO-dependent relaxation caused by electrical field stimulation (EFS) and acetylcholine (ACh) was studied, and the amplitude and duration of relaxation evaluated. RESULTS: The amplitude of relaxation induced by EFS was significantly decreased under physiological oxygen tension conditions (P < 0.01). The duration of the relaxant response induced by EFS and ACh was significantly prolonged in physiological oxygen tension conditions than in high oxygen tension (P < 0.01). However, there was no correlation between the duration of relaxation induced by EFS and each physiological oxygen tension level. The duration of relaxation induced by ACh was most prolonged at 60-69 mmHg oxygen tension. CONCLUSION: Physiologically, the effect of NO may last longer than was previously thought. In addition, it would seem that there is an optimal physiological oxygen tension for maximum ACh-induced relaxation.     

Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells

Granulocyte-colony stimulating factor (G-CSF) is known to induce proliferation and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malignant lymphoma or adult T-cell leukaemia/lymphoma (ATL). G-CSF is thought not to stimulate malignant lymphoid cells. In the present study we examined the ability of G-CSF to induce in vitro growth of primary ATL cells from 14 patients (nine acute-type, two chronic-type and three lymphoma-type), and we analysed the in vivo counts of ATL cells in patients who received G-CSF for neutropenia. FACS analysis using phycoerythrin-labelled recombinant G-CSF demonstrated that ATL cells from 11/14 patients express some G-CSF receptor (G-CSFR), with a range between 5.4% and 87.3%. Cells expressing G-CSFR also expressed CD4. Reverse polymerase chain reaction (PCR) analysis demonstrated expression of G-CSFR messenger RNA in G-CSFR expressing cells. Leukaemic cells derived from seven (four acute-type, one chronic-type and two lymphoma-type) of the 14 patients proliferated in vitro in response to G-CSF, as measured by [³H]thymidine incorporation; maximum responses were at G-CSF concentrations of 10–100 ng/ml. Nine of 14 patients receiving rG-CSF for neutropenia were analysed retrospectively for ATL cell numbers. Four patients whose primary tumour cells proliferated in response to rG-CSF in vitro showed a significant increase in ATL cell count after administration of rG-CSF ( P  =0.038), whereas five patients whose leukaemic cells did not proliferate in vitro showed no significant increase in ATL cell count. G-CSF can stimulate proliferation of ATL cells which may complicate therapy for this disease.     

Effect of cholestasis induced by organic anion on the lipid composition of hepatic membrane subfractions and bile in rats

Several organic anions inhibit the secretion of cholesterol and phospholipid into bile without affecting total bile acid secretion (uncoupling). The uncoupling induced by sulphobromophthalein (BSP) alters the fatty acid composition of biliary lecithin. The purpose of this study was to investigate the relationship between the lipid composition of bile and of liver subcellular membrane fractions during BSP-induced uncoupling. After depletion of the bile salt pool, rats fitted with a bile duct cannulus were infused with sodium taurocholate given either alone or with BSP. Bile was collected and liver microsomes and canalicular membranes were isolated for analysis of lipid composition. In bile, uncoupling increased the cholesterol/phospholipid ratio (C/P ratio) and the saturated/unsaturated fatty acid ratio (S/U ratio) in phosphatidylcholine. The C/P ratio was increased in the canalicular membrane, but the membrane phosphatidylcholine S/U ratio decreased during uncoupling. In microsomes, the S/U ratio of membrane phosphatidylcholine was slightly increased, but the C/P ratio was unaffected during uncoupling. These results support the hypothesis that an increased secretion of hydrophobic phosphatidylcholine species from the canalicular membrane into bile reduces the proportion of hydrophobic phosphatidylcholine species in the canalicular membrane during uncoupling. The decreased contribution of hydrophobic phosphatidylcholine species may ameliorate the decrease in membrane fluidity resulting from the accumulation of cholesterol in the canalicular membrane and stimulate the synthesis of hydrophobic phosphatidylcholine species in the microsomes.     

Cryoglobulinaemia among maintenance haemodialysis patients and its relation to hepatitis C infection

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.     

Dose-related protective efficacy of immunoglobulins in experimentally induced group B streptococcal infection

This study investigates the dose-dependent effect of administration of commercially available intravenous immunoglobulins (IVIG) on the survival of newborn rats experimentally infected with group B streptococci (GBS). The opsonic activity of various concentrations of IVIG in vitro was determined by examination of opsonophagocytosis of GBS by peritoneal macrophages and bacterial killing by blood neutrophils. The best survival was observed in newborn rats who received immunoglobulins at doses of 250, 500 and 1000 mg/kg of bodyweight. The survival of animals that received either 125 mg/kg or 2.5 g/kg of immunoglobulins was no better than that of animals who received no immunoglobulins. The maximal phagocytosis and bacterial killing were observed at in vitro immunoglobulin concentrations ranging from 32 to 250 mg/dL (these in vitro concentrations may correspond roughly to in vivo administration doses ranging from 150 to 1200 mg/kg). These doses are comparable to the doses of IVIG currently administered to neonates. However use of very high doses may be harmful to babies since the high concentration of non-specific immunoglobulins inhibited in vitro phagocytosis and bacterial killing by phagocytes.