Different outcomes after intracytoplasmic sperm injection without oocyte activation in two patients with different types of globozoospermia.

Different outcomes after intracytoplasmic sperm injection (ICSI) without oocyte activation in two patients with different types of round-headed spermatozoa (globozoospermia) are reported. After controlled ovarian hyperstimulation and oocyte pick-up, retrieved oocytes were underwent ICSI without oocyte activation and a 33.33% (4/12) fertilisation rate was obtained in the first case, whereas an abnormal fertilisation was achieved in the second case. The transfer of two grade II embryos in the first couple resulted in clinical pregnancy with a healthy livebirth. It was concluded that the main problem of cases with globozoospermia was a low fertilisation rate or failure fertilisation, and even though ICSI and artificial oocyte activation have been employed to increase this rate, it is not necessarily needed to achieve a pregnancy.

Optimal timing for collection of PBPC after glycosylated G-CSF administration.

Daily administration of granulocyte colony-stimulating Factor (G-CSF) results in progenitor cell mobilization with maximum blood levels achieved after 4-7 days. In this study the short-term effects of glycosylated G-CSF at a dose of 5 microg/kg s.c. were determined so as to allow optimization of the timing of progenitor cell collection. In the first study involving 20 normal volunteers, a significant fall in neutrophil count and G-CSF levels was observed 2 h after the G-CSF injection. To investigate this phenomenon serial measurements were made in a further six volunteers after the 6th daily injection of G-CSF. A fall in the neutrophil count occurred which was maximal at 1 h and recovered to baseline within 3 h. There was also a fall in CD34+ cells (P = 0.034), GM-CFC (P = 0.025) and BFU-E (P = 0.066) and recovery to baseline levels took 4-12 h. We conclude that glycosylated G-CSF should not be given immediately prior to stem cell collection.

Crossover study of the haematological effects and pharmacokinetics of glycosylated and non-glycosylated G-CSF in healthy volunteers.

A cross-over study of glycosylated and non-glycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 microg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P = 0.02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P=0.03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P=0.003). Serum concentrations of G-CSF achieved were significantly higher with the non-glycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.

Manganese toxicity in children receiving long-term parenteral nutrition.

BACKGROUND: In patients receiving long-term parenteral nutrition (PN), cholestatic disease and nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the normal homoeostatic mechanisms of the liver and gut are bypassed and the requirement for this trace element is not known; nor has it been certain whether hypermanganesaemia causes the cholestasis or vice versa. We explored the direction of effect by serial tests of liver function after withdrawal of manganese supplements from children receiving long-term PN. We also examined the relation between blood manganese concentrations and brain lesions, as indicated by clinical examination and magnetic resonance imaging (MRI). METHODS: From a combined group of 57 children receiving PN we identified 11 with the combination of hypermanganesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the remainder. MRI was done in two of these children. We also looked at manganese concentrations and MRI scans in six children who had received PN for more than 2 years without developing liver disease. FINDINGS: In the hypermanganesaemia/cholestasis group, four of the 11 patients died. In the seven survivors baseline whole-blood manganese was 615-1840 nmol/L, and after 4 months it had declined by a median of 643 nmol/L (p < 0.01). Over the same interval total bilirubin declined by a median of 70 mumol/L (p < 0.05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighted images, bilateral symmetrically increased signal intensity in the globus pallidus and subthalamic nuclei. Such changes were also seen in five other children--one from the hypermanganesaemia/cholestasis group and four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). INTERPRETATION: The cholestasis complicating PN is multifactorial, but these results add to the evidence that manganese contributes. In view of the additional hazard of basal ganglia damage from high manganese levels in children receiving long-term PN, we recommend a low dose regimen of not more than 0.018 mumol/kg per 24 h together with regular examination of the nervous system.

High lactate dehydrogenase level is associated with an adverse outlook in autografting for Hodgkin's disease.

Forty-two patients with relapsed or refractory Hodgkin's disease (HD) were treated with high-dose chemotherapy (BEAM regimen) followed by autologous bone marrow and/or peripheral blood progenitor cell (PBPC) rescue. There was one procedure-related death and the overall response rate at 6 months was 88% (95% confidence interval 78-98%). The 2 year overall and event-free survival was 81% (95% confidence interval 65-96%) and 74% (95% confidence interval 58-89%) respectively. Median follow-up was 33 months. The use of PBPC instead of marrow resulted in a significant shortening of the time to engraftment (P < 0.01). Multivariate analysis identified the pre-transplant LDH level as a highly significant factor in predicting overall survival (P = 0.007). The BEAM regimen is an effective conditioning schedule that is well tolerated but patients with a raised LDH at the time of transplant remain at high risk of early relapse and death due to disease.

Implementing a policy for pneumococcal prophylaxis in a haematology unit after splenectomy.

People who have had a splenectomy for any reason are 40 times more likely to have an overwhelming infection, especially pneumococcal infection, and 17 times more likely to suffer fatal sepsis. The incidence of such life threatening infections is reduced by prophylactic immunisation with polyvalent pneumococcal vaccine and long term antibiotic prophylaxis or instituting prompt antibiotic treatment in the event of fever. This haematology unit agreed a policy of immunisation and antibiotic prophylaxis in June 1988 for all patients undergoing elective splenectomy. The success of this policy was audited in July 1993 by a retrospective analysis of patients' case notes. Seventy four patients were identified as having had a splenectomy, 54 (73%) before June 1988, of whom only 13 (24%) had received both pneumococcal immunisation and antibiotic prophylaxis before implementation of the agreed policy. At the time of audit, 46/74 (62%) patients were recorded as having received immunisation and 64/74 (86%) as receiving antibiotic prophylaxis or a supply of antibiotics to take in the event of a fever. All but one of the 20 patients who had a splenectomy after June 1988, since implementation of the agreed policy, received immunisation and antibiotic prophylaxis. The authors conclude that establishment of a formal agreed policy for pneumococcal prophylaxis for patients undergoing splenectomy has improved the quality of care.

Listeria meningitis after bone marrow transplantation.

Over the past decade infections from food-borne Listeria monocytogenes have become an important cause of septicaemia and meningitis and immunocompromised patients are at particular risk. We report three cases of Listeria meningitis occurring post-BMT. The patients were aged 53, 51 and 56 years and presented 4, 7 and 90 months post-transplant, respectively. The first patient had undergone allogeneic BMT for myelodysplasia and the other two patients had ABMT for AML in second and first CR, respectively. All the patients presented with classical features of meningitis and L. monocytogenes was cultured from cerebrospinal fluid. All made a full recovery with appropriate antibiotic therapy. We have not seen cases of meningitis due to other organisms in our transplant programme and the cases represent a risk of one episode per 59 surviving patient years. None of the patients was receiving prophylactic post-BMT antibiotics and the episodes may strengthen the case for using prophylactic penicillin. Recent epidemics of septicaemia and meningitis caused by L. monocytogenes-contaminated milk and cheese suggest that these patients should be informed about potential sources of infection.

BEAM autografting in lymphoma--experience at one centre.

Since December 1987, we have examined the use of high-dose chemotherapy and unpurged bone marrow rescue in 31 patients with advanced or refractory lymphoma. Twenty-one patients had Hodgkin's disease (HD) and 10 had Non-Hodgkin's lymphoma (NHL). At ABMT, 22 patients had relapsed or resistant disease. All patients, excluding 3 early deaths, engrafted. There was no relationship between cell numbers harvested, CFU-GM and bone marrow recovery. The mean times to 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets were 20 d and 43 d respectively. However, 5 patients with HD had a significantly slower platelet recovery time of up to 203 days (p = 0.05). Disease-free survival was 72% for HD and 40% for NHL at 40 months. Relapsed or refractory disease at ABMT, bulky disease, extensive salvage therapy and Karnofsky scores below 80% were all associated with a poorer outcome. The most striking observation has been the dramatic radiological response of some patients with advanced/refractory disease.