The effect of chemotherapy on the kinetics and proliferative capacity of normal and tumorous tissues in vivo

The proliferative state of a given tissue is a major determinant of its sensitivity to both phase-specific and cycle-specific chemotherapeutic agents. To study the extent of injury induced by antitumor agents to normal and tumorous tissues, a technique for following DNA synthesis as reflected in the incorporation of tritiated thymidine (3H-TdR) into DNA was compared to the conventional radioautographic technique of the labeling index (LI) and to the functional kinetic technique of granulocyte colony formation in vitro. Alterations in DNA synthesis induced by a single dose of cyclophosphamide in normal and tumorous tissues in vivo paralleled in many respects the changes seen when the more time-consuming techniques of the LI or granulocyte colony formation were employed. However, the recovery of granulocyte colony formation after cyclophosphamide therapy lagged behind the recovery of DNA synthesis in the bone marrow, obscuring a kinetic event of potential therapeutic significance. The determination of DNA synthesis simultaneously in normal and tumorous tissues in vivo was easy to perform and supplied therapeutically pertinent results comparatively quickly.     

The kidneys in paroxysmal nocturnal hemoglobinuria

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.     

Biochemical markers of bone turnover in seronegative spondylarthropathy: relationship to disease activity

To investigate bone turnover in patients with seronegative spondylarthropathy, a bone formation marker, type 1 procollagen carboxy- terminal propeptide (P1CP), and resorption markers, the pyridinium cross-links of collagen [urinary free (f) PYR and DPYR], were measured. The median f-PYR, f-DPYR and P1CP (+/-interquartile range) were 15.8 (6.00) nmol/mmol creatinine, 3.8 (2.2) nmol/mmol creatinine and 101.5 (38) micrograms/1, respectively. There was a positive correlation between resorption markers and acute-phase reactants such as C-reactive protein (r = 0.42 for PYR, r = 0.42 for DPYR, P < 0.05), and a negative correlation observed between P1CP and the erythrocyte sedimentation rate (r = -0.64, P < 0.05). In the subgroup of patients with an elevated CRP concentration, the concentration of PYR and DPYR was significantly increased (f-PYR 25.7 vs 15.8 and f-DPYR 6.6 vs 3.8, P < 0.01 for f-PYR, P < 0.05 for f-DPYR). This study suggests than an elevation in acute-phase response in patients with seronegative spondylarthropathy is associated with increased concentration of bone resorption markers with a tendency for reduction in bone formation markers. This may represent uncoupling of bone formation and resorption, leading to bone loss in such patients.      

Outcomes for patients with infantile idiopathic scoliosis by casting table type

Purpose:Serial casting is an effective treatment for infantile idiopathic scoliosis. The most common casting table types are Mehta, Risser, and spica tables. We compared major curve correction between patients with infantile idiopathic scoliosis treated using pediatric hip spica tables versus Risser or Mehta tables.Methods:In this multicenter retrospective study, we included 52 children younger than 3 years (mean ± standard deviation age, 1.6 ± 0.68 years) treated with ≥2 consecutive casts for infantile idiopathic scoliosis between September 2011 and July 2018. We compared major curve angle (measured using the Cobb method) before and after treatment and improvement in curve angle between the spica tables group (n = 12) and the Risser or Mehta tables group (n = 40). The primary outcome was the difference in percentage correction of the major curve according to radiographs taken after first casting and at final follow-up.Results:The mean major curve was 47° ± 18° before casting. A median of six casts (range: 2–14) were applied. Mean follow-up after treatment initiation was 22 months (range: 7–86 months). At baseline, the major curve was significantly larger in the spica tables group (58°) than in the Risser or Mehta tables group (43°) (p = 0.01). We found no differences in the percentage curve correction in the spica tables group versus Risser or Mehta tables group after first casting or at final follow-up.Conclusion:Serial casting was associated with substantial major curve correction in patients with infantile idiopathic scoliosis. Curve correction did not differ between patients treated with a spica table versus a Risser or Mehta table.Level of Evidence:Level III, retrospective cohort study     

A time–motion study of digital radiography at implementation

With increasing budgetary restraints on the health system, it is apparent that the main contribution that radiology departments can make to significant cost reduction in hospitals is to decrease the length of time between requesting an X-ray examination and receiving the report (and images). Digital radiography (DR) was introduced into the Radiology Department at the Royal Adelaide Hospital as a pilot project to research the cost–benefits and efficiency of the system, and to determine future directions for planning a digital department. The business plan developed prior to implementation of this pilot project predicted a saving of one bed-day per inpatient when a fully digital department with a picture archiving and communication system (PACS) is installed. This initial study comparing DR and conventional radiography (convR) provides baseline data and shows encouraging results for more rapid transmission of reports to clinicians.     

Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

The Kheda malaria project: the case for environmental control

The Kheda project experience has shown that bio-environmentalcontrol of malaria is feasible, cost effective and ecologicallysound. It clearly brings out the need to consider health issuesat the planning stage of all developments. Bio-environmentalcontrol of malaria is suggested as the first line of attackfor the control of mosquitoes, malaria and other mosquito-bornediseases. Insecticides may be reserved for short-term use. Thiswill enable judicious and selective use of insecticides in solelyepidemic situations. The growing problem of resistance to insecticidesin mosquitoes as well as environmental pollution, can then besolved on a long term basis.