Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.     

Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein.

The major surface glycoprotein (G) of human respiratory syncytial (RS) virus has an estimated mature Mr of 84,000-90,000. Among a library of cDNA clones prepared from RS virus mRNAs, we identified clones that hybridized to a message that encoded a Mr 36,000 polypeptide that was specifically immunoprecipitated with anti-G antiserum. The amino acid sequence of the G protein backbone was determined by nucleotide sequence analysis of several of the cDNA clones. It contains a combination of structural features that make it unique among the known viral glycoproteins. The G mRNA is 918 nucleotides long and contains a single major open reading frame that encodes a polypeptide having 298 amino acid residues with a Mr of 32,587, a finding consistent with the Mr 36,000 estimate for the in vitro translation product of the G mRNA. This suggests that greater than 50% of the molecular weight of the mature glycoprotein may be contributed by carbohydrate. Glycosylation of G is largely resistant to tunicamycin, an inhibitor of the attachment of N-linked oligosaccharides, suggesting that the majority of the carbohydrate residues are attached via O-glycosidic bonds. In accordance with this, serine and threonine residues, the acceptor sites for O-linked oligosaccharides, comprise 30.6% of the total amino acid composition. There are also four potential acceptor sites for N-linked oligosaccharides. The amino acid sequence lacks both an NH2-terminal hydrophobic signal sequence and a COOH-terminal hydrophobic region. Instead, a strongly hydrophobic region is located between amino acid residues 38 and 66. This region may serve as both the signal to insert the nascent polypeptide through the membrane and as the membrane anchor site.     

Humidification devices

Humidification is a process of adding water vapour to a volume of one or more gases. Natural humidification is achieved in the nasal cavity, but this process is often bypassed during anaesthesia and critical care. Various devices are used for artificial humidification the commonest being the heat and moisture exchanger, often combined with a microbial filter. Electrically heated water baths and other devices are discussed.     

Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

Atherosclerotic axillary artery aneurysm

True aneurysms of the axillary artery are rare, most pulsatile masses in the region being pseudoaneurysms. The present study reports a case of a true atherosclerotic axillary artery aneurysm arising in a 65 year old lady which presented with a short history of a painless pulsatile mass and sensory defecit in the hand in the absence of limb trauma. Following preoperative imaging to determine the anatomic details, she underwent repair of the aneurysm and made an excellent symptomatic recovery.     

Noncompliance with seat-belt use in patients involved in motor vehicle collisions.

BACKGROUND: Seat-belt compliance in trauma patients involved in motor vehicle collisions (MVCs) appears low when compared with compliance of the general public. In this study we wished to define the relative frequency of seat-belt use in injured Canadian drivers and passengers and to determine if there are risk factors particular to seat-belt noncompliance in this cohort. METHODS: We identified trauma patients who were involved in MVCs over a 24-month period and contacted them 2-4 years after the injury by telephone to administer a standardized survey. Potential determinants of seat-belt noncompliance were compared with the occurrence of an MVC by multiple logistic regression. RESULTS: Seat-belt noncompliance in 386 MVC patients was associated with drinking and driving, youth, speeding, male sex, being a passenger, smoking, secondary roads, rural residence, low level of education, overnight driving, having no dependents, licence demerit points, previous collisions, unemployment and short journeys. There was an increase in seat-belt awareness and a decrease in self-rated driving ability after the MVC. CONCLUSIONS: Factors that indicate poor driving habits (alcohol, speeding, previous MVCs and driving offences) also predict seat-belt noncompliance. Injury prevention programs should selectively target these high-risk drivers to improve seat-belt compliance and limit associated injury and consumption of health care resources.     

Long‐Term Controlled Normoglycemia in Diabetic Non‐Human Primates After Transplantation with hCD46 Transgenic Porcine Islets

Xenotransplantation of porcine islets into diabetic non‐human primates is characterized by (i) an initial massive graft loss possibly due to the instant blood‐mediated inflammatory reaction and (ii) the requirement of intensive, clinically unfriendly immunosuppressive therapy. We investigated whether the transgenic expression of a human complement‐regulatory protein (hCD46) on porcine islets would improve the outcome of islet xenotransplantation in streptozotocin‐induced diabetic Cynomolgus monkeys. Immunosuppression consisted of thymoglobulin, anti‐CD154 mAb for costimulation blockade, and mycophenolate mofetil. Following the transplantation of islets from wild‐type pigs (n = 2) or from 1,3‐galactosyltransferase gene‐knockout pigs (n = 2), islets survived for a maximum of only 46 days, as evidenced by return to hyperglycemia and the need for exogenous insulin therapy. The transplantation of islets from hCD46 pigs resulted in graft survival and insulin‐independent normoglycemia in four of five monkeys for the 3 months follow‐up of the experiment. One normalized recipient, selected at random, was followed for >12 months. Inhibition of complement activation by the expression of hCD46 on the pig islets did not substantially reduce the initial loss of islet mass, rather was effective in limiting antibody‐mediated rejection. This resulted in a reduced need for immunosuppression to preserve a sufficient islet mass to maintain normoglycemia long‐term.     

How COVID-19 Patients Were Moved to Speak: A Rehabilitation Interdisciplinary Case Series

Background

Up to 36% of patients admitted to the ICU for COVID-19 require tracheostomy. While the literature recommends the use of multidisciplinary teams in the management of patients with tracheostomy for other diseases, little is known on the collaborative administration of physical therapy and speech language pathology services in the COVID-19 population.

Purpose

We sought to determine the outcomes of a collaboration between physical therapy (PT) and speech language pathology (SLP) in the treatment of patients who underwent tracheostomy placement as part of their treatment for COVID-19 at our facility.

Methods

We conducted a retrospective case series on patients with COVID-19 who had a tracheostomy. We included patients who had undergone mechanical ventilation for 14 days or longer, had a surgical tracheostomy, been discharged from intensive care to a medical unit, and received PT and SLP referrals. We compiled retrospective data from electronic medical records, analyzing days from tracheostomy to achievement of PT and SLP functional milestones, including mobility, communication, and swallowing. Of six critically ill patients with COVID-19 who had tracheostomy placement at our facility, three met inclusion criteria: patient 1, a 33-year-old woman; patient 2, an 84-year-old man; and patient 3, an 81-year-old man. For all patients, PT interventions focused on breathing mechanics, secretion clearance, posture, sitting balance, and upper and lower extremity strengthening. SLP interventions focused on cognitive reorganization, verbal and nonverbal communication, secretion management, and swallowing function. Intensity and duration of the sessions were adapted according to patient response and level of fatigue.

Results

We found that time to tracheostomy from intubation for the three patients was 23 days, 20 days, and 24 days, respectively. Time from tracheostomy insertion to weaning from ventilator was 9 days for patient 1, and 5 days for patient 2 and patient 3. Regarding time to achieve functional PT and SLP milestones, all patients achieved upright sitting with PT prior to achieving initial SLP milestone of voicing with finger occlusion. Variations in progression to swallowing trials were patient specific and due to respiratory instability, cognitive deficits, and limitations in production of an effortful swallow. Patient participation in therapy sessions improved following establishment of oral verbal communication.

Conclusion

Interdisciplinary cooperation and synchronized implementation of PT and SLP interventions in three COVID-19 patients following prolonged intubation facilitated participation in treatment and achievement of functional milestones. Further study is warranted.