Second marrow transplants in patients with aplastic anemia rejecting the first graft: use of a conditioning regimen including cyclophosphamide and antithymocyte globulin

Sixteen (11%) of 146 consecutive patients with severe aplastic anemia prepared for engraftment with cyclophosphamide (200 mg/kg) rejected marrow grafts from their HLA-identical siblings. They were given a second marrow transplant from either the same (n = 13) or a second (n = 3) HLA-identical sibling between 23 and 743 (median 86) days after the first transplant. The preparation for the second transplant included cyclophosphamide, 50 mg/kg, on each of four successive days. Twelve hours after each of the first three doses of cyclophosphamide, antithymocyte globulin, 30 mg/kg/dose, was infused. One of the 16 patients died from infection too early after the second transplant to be evaluated, two had failure of engraftment and died with infection, one rejected the second graft and is surviving almost 5 years later with full autologous marrow recovery, and 12 had successful and sustained second grafts. Of these 12, six are surviving between 11 months and 7 3/4 years. Four of the six have no graft-v-host disease (GVHD), while two have chronic GVHD requiring treatment. Five have Karnofsky scores of 100% and one of 90%. Six of the 12 patients with sustained grafts died between 63 days and 38 months after transplantation, four with infections (related in two patients to chronic GVHD), one with acute GVHD, and one with hemorrhage. The average interval from first to second transplant was 308 days during the past five years, compared to 61 days in earlier patients. Five of seven recent patients are surviving, compared to two of nine earlier patients. In conclusion, successful second transplants after cyclophosphamide and antithymocyte globulin are possible in most patients with aplastic anemia who have rejected their first marrow grafts; however, mortality remains high, with only 40% of the patients becoming long-term survivors.     

Transient bone marrow oedema: A variant pattern of sacral insufficiency fractures

A 71-year-old woman presenting with severe low back pain was found to have a large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images, highly suggestive of malignancy. Open biopsies showed only callus formation. The patient responded clinically to conservative measures, with twice-repeated follow-up Tc-99m MDP and MR scans documenting resolution of transient bone marrow oedema. We suggest that this form of marrow oedema represents a variant pattern of sacral insufficiency fractures.     

Evaluation of a rapid stoolantigen test for the diagnosis of Helicobacter pylori infection in Chinese patients

OBJECTIVE: To evaluate the accuracy of a rapid assay that wasdeveloped to detect Helicobacter pylori antigen in the stool,using the principle of immunochromatography, in the Chinese population. METHODS: Eligible patients without prior treatment of H.pylori were recruited. An in‐house rapid urease test (RUT) andhistology were used as the gold standard. The results of the rapidstool antigen test were compared with the gold standard. RESULTS: Valid rapid stool antigen test results for interpretationwere obtained from 94 consecutive patients (mean age: 52.5, range:22?82 years). Sensitivity, specificity, positive predictivevalue, negative predictive value and accuracy were, respectively, 77.5%,87.0%, 81.6%, 83.9% and 83.0%.The test was easy to perform and results were available within 15 min. CONCLUSION: The rapid stool antigen test using immunochromatography accuratelydiagnoses H. pylori infection in Chinese patients.     

Robotic urological surgery in patients with prior abdominal operations is not associated with increased complications

BACKGROUND: The da Vinci Surgical Robotic System is being increasingly used to perform complex urological operations by minimally invasive techniques. Prior abdominal surgery associated with intra-abdominal adhesions may complicate robotic surgery. METHODS: We used a cohort of consecutive 49 patients undergoing a variety of robotic urological procedures at our institution to study the impact of prior abdominal operations on early perioperative complications. RESULTS: A total of 21/49 (43%) patients (Group A) had no history of prior abdominal surgery and the rest 28/49 (57%; Group B) had undergone prior abdominal surgery. The incidence of peritoneal adhesions was significantly higher in patients with prior abdominal surgery compared to the rest of the cohort, 54% versus 10% (P=0.002). The median operative time, estimated blood loss, postoperative drop in hemoglobin, time to hospital discharge, postoperative narcotic analgesic use and postoperative complication rate between group A and group B were not statistically different. The overall perioperative complication rate for the entire cohort was 14.3%, with 6-8% of complications occurring in each of the two groups (P=1.0). Comparative subset analysis of 28 patients in Group B, 15 (54%) and 13 (46%) with or without intra-abdominal adhesions did not reveal a significant difference in perioperative complication rates either. However, operative time was longer in patients with intra-abdominal adhesions compared to patients without, median of 590 (281-922) and 434 (153-723) min respectively, although not statistically significant (P=0.059). CONCLUSION: Our study demonstrates that robotic urological surgery can be performed in patients with prior abdominal surgery without increased perioperative complications.     

Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East

Walker-Warburg syndrome (WWS) is a genetically heterogeneous autosomal recessive disease characterized by congenital muscular dystrophy, cobblestone lissencephaly, and ocular malformations. Mutations in six genes involved in the glycosylation of á-dystroglycan (POMT1, POMT2, POMGNT1, FCMD, FKRP and LARGE) have been identified in WWS patients, but account for only a portion of WWS cases. To better understand the genetics of WWS and establish the frequency and distribution of mutations across WWS genes, we genotyped all known loci in a cohort of 43 WWS patients of varying geographical and ethnic origin. Surprisingly, we reached a molecular diagnosis for 40% of our patients and found mutations in POMT1, POMT2, FCMD and FKRP, many of which were novel alleles, but no mutations in POMGNT1 or LARGE. Notably, the FCMD gene was a more common cause of WWS than previously expected in the European/American subset of our cohort, including all Ashkenazi Jewish cases, who carried the same founder mutation.     

Out of Pocket Expenditure for Sick Newborn Care in Referral Hospitals of Nepal

Background

Almost all preventable neonatal deaths take place in low- and middle-income countries and affect the poorest who have the least access to high quality health services. Cost of health care is one of the factors preventing access to quality health services and universal health coverage. In Nepal, the majority of expenses related to newborn care are borne by the caregiver, regardless of socioeconomic status. We conducted a study to assess the out of pocket expenditure (OOPE) for sick newborn care in hospitals in Nepal.

Methods

This cross-sectional study of hospital care for newborns was conducted in 11 hospitals in Nepal and explored OOPE incurred by caregivers for sick newborn care. Data were collected from the caregivers of the sick newborn on the topics of cost of travel, accommodation, treatment (drugs, diagnosis) and documented on a sick newborn case record form.

Results

Data were collected from 814 caregivers. Cost of caregivers’ stay accounted for more than 40% of the OOPE for sick newborn care, followed by cost of travel, and the baby’s stay and treatment. The overall OOPE ranged from 13.6 to 226.1 US dollars (USD). The median OOPE was highest for preterm complications ($33.2 USD; CI 14.0–226.1), followed by hyperbilirubinemia ($31.9 USD; CI 14.0–60.7), respiratory distress syndrome ($26.9 USD; 15.3–121.5), neonatal sepsis ($ 25.8 USD; CI 13.6–139.8) and hypoxic ischemic encephalopathy ($23.4 USD; CI 13.6–97.7).

Discussion for practice

In Nepal, OOPE for sick newborn care in hospitals varied by neonatal morbidity and duration of stay. The largest proportion of OOPE were for accommodation and travel. Affordable and accessible health care will substantially reduce the OOPE for sick newborn care in hospitals.

     

The effects of amphetamine on neuromuscular transmission in the lobster

In vitro electrophysiological techniques were used on an excitatory neuromuscular junction of a walking-limb stretcher muscle of the lobster in order to define the pharmacology of amphetamine on a glutamatergic synapse. A single electrical stimulus in the presence of the drug produced a train of action potentials in the axon innervating the neuromuscular junction, resulting in a staircase-like enhancement of the evoked excitatory junction potential; both effects were antagonized by relatively small doses of haloperidol. In contrast, amphetamine reduced the amplitude of the spontaneous miniature junctional potential, suggesting a postsynaptic site of action; this depressant response to the drug was not antagonized by haloperidol. The data demonstrate that amphetamine concomitantly produces both excitation and depression at a single synapse.