Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis

We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.     

Biliary, Pancreatic, and Sphincter of Oddi Electrical and Mechanical Signals Recorded During ERCP

Measurements of biliary tract motility havefocused on radiologic and pressure measurements toquantify biliary motility rather than measurements ofelectrical activity of the biliary tract. We previously reported the recording of biliary electricalsignals during ERCP and now report on the continueddevelopment and validation of a system to measurebiliary tract electrical activity as well as biliarymechanical activity. In 26 patients presenting with avariety of clinical indications, we recordedmeasurements of electrical activity from the common bileduct sphincter (16 patients), pancreatic duct sphincter(eight patients), and/or sphincter of Oddi (eightpatients). Electrical recordings were performed with aspecially modified ERCP catheter, using two circularelectrodes as well as a custom catheter that measured both electrical and mechanical activity.Electrical activity of the biliary tract wassuccessfully recorded in 25 of 26 patients (96%),including the common bile duct sphincter (16 patients,62%), pancreatic duct sphincter (eight patients, 31%) andsphincter of Oddi (eight patients, 31%). Along with theelectrical recordings, common bile duct sphinctermechanical activity was recorded in 12 patients (67%), pancreatic duct sphincter mechanical activityin six patients (33%), and sphincter of Oddi mechanicalactivity in six patients (33%). Frequency analysis ofelectrical signals revealed a mean frequency(cycles/min) of 4.7 ± 0.5 in the common bile ductsphincter, 4.1 ± 0.6 in the pancreatic ductsphincter, and 4.9 ± 0.7 in the sphincter ofOddi. Phasic mechanical frequency in cycles per minutewas recorded at a frequency of 4.8 ± 0.5 in common bileduct sphincter, 4.0 ± 0.6 in pancreatic ductsphincter, and 5.3 ± 0.9 in sphincter of Oddi.Tonic pressure (averaged 12.1 ± 1.5 mm Hg) incommon bile duct sphincter, 12.4 ± 1.4 mm Hg inpancreatic duct sphincter, and 15.0 ± 5.1 mm Hgin sphincter of Oddi. Analysis of wave form propagations(noted as percentage antegrade, retrograde, orindeterminant) revealed 50% antegrade, 23% retrograde, and 27%indeterminant). One patient was recorded on twooccasions via ERCP; the same patient had anintraoperative recording. All three recordings showedsimilarities. We conclude that measurements of biliary,pancreatic, and sphincter of Oddi electrical andmechanical activity are feasible and can be done as partof ERCP. There was good correlation between biliarytract electrical and mechanical events and differentwave form characteristics were noted for different partsof the biliary tree. Further studies are warranted toevaluate the potential usefulness of measurement of biliary tract electrical activity, and toconfirm its correlation with mechanical events in thepancreato-biliary tree.     

Western blot analysis of serological responses following immunization with vaccinia viral lysates of melanoma cells

Western blot analysis was used to characterize the antibody response of melanoma patients during immunization with vaccinia-virus-induced melanoma cell lysates (VMCL). Strong antibody responses were detectable within 4 weeks from commencement of immunization against different fractions (from 3 to 10) in blots of VMCL. The approximate MW of the main fractions identified were 100, 91, 85, 77, 64-66, 49, 46, 43 and 34-36 kDa. Comparison of the reactivity of the sera with extracts of vaccinia virus suggested that the reactivity against VMCL was not against viral antigens in the lysates. Studies on autologous extracts from 7 patients immunized with VMCL indicated that the majority of the fractions identified in extracts of VMCL were also identified in autologous extracts of melanoma cells. This indicated vaccine-induced responses against the patients' tumor cells and not merely against alloantigens in the vaccine. Sera from the immunized patients appeared to identify a number of fractions of similar MW in extracts of colon and glioma cells, suggesting that the responses were not specific for melanoma. Possible exceptions were reactivity against melanoma fractions of 85, 64-66 and 36 kDa. Our studies provide evidence for the effectiveness of VMCL in inducing antibody responses against autologous melanoma cells and form a basis for subsequent biochemical and genetic analysis of the antigens identified by antibody responses in immunized patients.     

Global cost of correcting vision impairment from uncorrected refractive error

Objective

To estimate the global cost of establishing and operating the educational and refractive care facilities required to provide care to all individuals who currently have vision impairment resulting from uncorrected refractive error (URE).

Methods

The global cost of correcting URE was estimated using data on the population, the prevalence of URE and the number of existing refractive care practitioners in individual countries, the cost of establishing and operating educational programmes for practitioners and the cost of establishing and operating refractive care facilities. The assumptions made ensured that costs were not underestimated and an upper limit to the costs was derived using the most expensive extreme for each assumption.

Findings

There were an estimated 158 million cases of distance vision impairment and 544 million cases of near vision impairment caused by URE worldwide in 2007. Approximately 47 000 additional full-time functional clinical refractionists and 18 000 ophthalmic dispensers would be required to provide refractive care services for these individuals. The global cost of educating the additional personnel and of establishing, maintaining and operating the refractive care facilities needed was estimated to be around 20 000 million United States dollars (US$) and the upper-limit cost was US$ 28 000 million. The estimated loss in global gross domestic product due to distance vision impairment caused by URE was US$ 202 000 million annually.

Conclusion

The cost of establishing and operating the educational and refractive care facilities required to deal with vision impairment resulting from URE was a small proportion of the global loss in productivity associated with that vision impairment.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.     

Medial patellofemoral ligament reconstruction in patellar instability

Background:

Medial patellofemoral ligament (MPFL) is one of the major static medial stabilising structures of the patella. MPFL is most often damaged in patients with patellar instability. Reconstruction of MPFL is becoming a common surgical procedure in treating patellar instability. We hypothesised that MPFL reconstruction was adequate to treat patients with patellar instability if the tibial tubercle and the centre of the trochlear groove (TT-TG) value was less than 20 mm and without a dysplastic trochlea.

Materials and Methods:

30 patients matching our inclusion criteria and operated between April 2009 and May 2011 were included in the study. MPFL reconstruction was performed using gracilis tendon fixed with endobutton on the patellar side and bio absorbable interference screw or staple on the femoral side. Patients were followed up with subjective criteria, Kujala score and Lysholm score.

Results:

The mean duration of followup was 25 months (range 14-38 months). The mean preoperative Kujala score was 47.5 and Lysholm score was 44.7. The mean postoperative Kujala score was 87 and Lysholm score was 88.06. None of the patients had redislocation.

Conclusion:

MPFL reconstruction using gracilis tendon gives excellent results in patients with patellar instability with no redislocations. Some patients may have persistence of apprehension.