Nonparametric models and methods for designs with dependent censored data: part I.

We consider a nonparametric (NP) approach to the analysis of repeated measures designs with censored data. Using the NP model of Akritas and Arnold (1994, Journal of the American Statistical Association 89, 336-343) for marginal distributions, we present test procedures for the NP hypotheses of no main effects, no interaction, and no simple effects. This extends the existing NP methodology for such designs (Wei and Lachin, 1984, Journal of the American Statistical Association 79, 653-661). The procedures do not require any modeling assumptions and should be useful in cases where the assumptions of proportional hazards or location shift fail to be satisfied. The large-sample distribution of the test statistics is based on an i.i.d. representation for Kaplan-Meier integrals. The testing procedures apply also to ordinal data and to data with ties. Useful small-sample approximations are presented, and their performance is examined in a simulation study. Finally, the methodology is illustrated with two real life examples, one with censored and one with missing data. It is indicated that one of the data sets does not conform to any set of assumptions underlying the available methods and also that the present method provides a useful additional analysis even when data sets conform to modeling assumptions.

Neuropathic gait shows only trends towards increased variability of sagittal plane kinematics during treadmill locomotion.

Patients with diabetes mellitus (DM) and peripheral neuropathy (PN) are at greater risk of falling and of suffering injuries during falls. It has been hypothesized that PN leads to changes in gait variability that may account for this increased risk. The purpose of this investigation was to analyze the variability of the sagittal plane kinematics of diabetic neuropathic (NP), diabetic non-neuropathic (NNP) and age- and weight-matched control subjects (Control) during motorized treadmill walking at constant speed. While there were distinct trends towards increased variability within the three diagnostic groups (NP > NNP > Control) for several measures of gait variability, most of these trends were not statistically significant. We hypothesize that motorized treadmill walking may be inherently less variable than overground walking and that statistical measures of variability may not be sufficient to fully characterize stride-to-stride variability in human locomotion.

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women.

This investigation examined effects of chronic (>/=2 yr) hormone replacement therapy (HRT), both estrogen replacement therapy (ERT) and estrogen plus progesterone therapy (E+P), on core temperature and skin blood flow responses of postmenopausal women. Twenty-five postmenopausal women [9 not on HRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for 1 h at an ambient temperature of 36 degrees C. Cutaneous vascular conductance (CVC) was monitored by laser-Doppler flowmetry, and forearm vascular conductance (FVC) was measured by using venous occlusion plethysmography. Iontophoresis of bretylium tosylate was performed before exercise to block local vasoconstrictor (VC) activity at one skin site on the forearm. Rectal temperature (Tre) was approximately 0.5 degrees C lower for the ERT group (P < 0.01) compared with E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (Tb) and CVC: Tb curves were shifted approximately 0.5 degrees C leftward for the ERT group (P < 0.0001). Baseline CVC was significantly higher in the ERT group (P < 0.05), but there was no interaction between bretylium treatment and groups once exercise was initiated. These results suggest that 1) chronic ERT likely acts centrally to decrease Tre, 2) ERT lowers the Tre at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition of exogenous progestins in HRT effectively blocks these effects.

Radiographic changes of the jawbones in end stage renal disease.

Thirty-eight patients with a history of end stage renal disease (ESRD) were evaluated with panoramic and periapical radiographs for changes in lamina dura, trabecular pattern, radiographic density, and pulp chamber size, as well as the presence of radiolucent lesions not associated with the roots of teeth. Partial or complete loss of lamina dura, delicate of absent trabecular patterns, and an overall granular or chalky white appearance associated with an increase in radiographic density were the most common alterations. These tended to occur together and were most easily observed in the lower molar area superior to the mandibular canal. Radiolucent lesions not associated with the roots of teeth, expansion of alveolar ridges, and radiographic loss of the cortical borders of the maxillary sinus, nasal floor, and mandibular canal were less common but were occasionally noted. Multiple correlation coefficients between radiographic changes and selected biomedical patient data were obtained by computer analysis, and their significance discussed. The pathogenesis of end stage renal disease was also reviewed.

Hemodialysis and renal transplantation in patients with hypernephroma.

Of five patients with hypernephroma who were maintained on hemodialysis after nephrectomy, four died with metastic disease after having been on hemodialysis for an average of 13.7 months (range 8 to 19). The fifth patient had no evidence of malignancy after 21 months of dialysis; he then received a renal allograft from his sister, and did well for 24 months before he developed liver metastasis. We believe hemodialysis is an appropriate mode of treating the renal failure of patients with hypernephroma after therapeutic nephrectomy. These patients may be considered for renal transplantation after a period of hemodialysis, and we suggest the currently recommended 12-month waiting period before transplantation be extended to 18 to 24 months. Use of living related donor renal allograft in these patients is questionable.

Serum ferritin level. Determinant of iron requirement in hemodialysis patients.

Seventeen patients without renal failure and 14 patients receiving long-term hemodialysis were studied. Serum and bone marrow ferritin determinations were made at the time of bone marrow aspiration. A good correlation was found between serum ferritin levels and bone marrow iron stores, as well as between bone marrow ferritin levels and iron stores. Serum ferritin determinations appear to give an accurate estimation of bone marrow iron stores, thereby providing a reliable guide for iron replacement therapy and reducing the need for repeated bone marrow aspirations. Serum ferritin levels of less than 105 ng/ml suggest decreased iron stores, and values greater than 120 ng/ml indicate adequate or increased iron stores. Preliminary data also suggest that bone marrow ferritin determinations may be useful in quantitating bone marrow iron stores.

Clinical evaluation of patients dialysed with double Gambro 4 hours, three times per week.

To reduce the hours and cost of each dialysis and/or to increase adequacy of haemodialysis treatment 14 chronic dialysis patients were dialysed with two Gambro dialysers, 4 hr for 3 days per week. General well-being, anaemia, and nerve conduction velocity improved in some patients during the study period. Increasing dialysis surface area by using two Gambro dialysers enabled reduction of hours of dialysis, which was favourably accepted by all patients and decreased cost of dialysis, mainly by increasing the capacity of a unit to dialyse more patients with the same personnel and equipment.