Survival, disease progression and prognostic factors in elderly patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of 174 patients.

BACKGROUND: Advanced age at diagnosis is considered a poor prognostic factor in mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the outcomes and prognostic factors in patients diagnosed at an advanced age (≥65 years) with MF/SS. METHODS: Survival, progression rates and various clinical and histopathological variables were studied in a group of 174 elderly patients diagnosed with MF/SS between 1992 and 2015 at a single referral cancer center in the United States. Kaplan-Meier estimates were used to determine survival and progression and Cox proportional hazards regression univariate and multivariate models were used to identify prognostic factors. RESULTS: Of 174 elderly patients, 76.4% were diagnosed with early-stage (clinical stages IA-IIA) and 23.6% with late-stage MF/SS (IIB-IV). Advanced age was associated with poor overall survival, but not with disease-specific survival (DSS) or progression-free survival (PFS). Gender, increasing clinical stage, T and B classifications, elevated lactate dehydrogenase (LDH) levels and development of large cell transformation (LCT) were significant predictors of poor survival or disease progression. Patients with early-stage MF and <10% total skin involvement (T1 classification) or patch-only disease (T1a/T2a) showed better PFS with no observed disease-specific mortality. Folliculotropic MF was associated with poor DSS in patients with early-stage disease. CONCLUSIONS: Older age at diagnosis of MF/SS does not predict worse disease-specific outcomes. Elderly patients with early-stage disease, specifically involving less than 10% of the skin surface with patches but without plaques or folliculotropism, have an excellent prognosis. However, the development of LCT is a strong prognostic indicator of poor survival in elderly patients with MF/SS.

Thallium-201 for medical use. II: Biologic behavior.

Thallium-201 has been evaluated for myocardial imaging by determining its distribution and assessing its imaging properties. Organ distribution with time was studied in goats, chosen for their large size and easy operability. Myocardial imaging was performed in living and sacrificed goats and also in two anesthetized dogs, without infarction. Infarcts were made by ligature at open chest surgery on the goats and the infarcts subsequently confirmed histologically. The myocardium of normal and infarced, young and old goats was cut into blocks and the isotope distribution measured and compared with that in the lungs, liver, spleen, and kidney in normal goats. The renal medulla-to-cortex concentration ratio in goats was studied and is approximately five. The heart uptake exceeds 3% for 100 min whereas contiguous organs have less than one-half of the myocardial concentration, and blood clearance is rapid. One problem may prove to be inhomogeneity of uptake of thallium in the "normal" myocardium, showing a standard deviation of 1u% in a young goat and 29% in an old goat. In view of the good myocardial uptake, however, this work strongly suggests the trial 201Tl in patients.

Thallium-201 for medical use. Part 3: Human distribution and physical imaging properties.

Studies were undertaken to determine the biologic distribution of thallium-201 in man. The disappearance from the blood is extremely rapid and intracellular deposition is nearly immediate. The biologic half-time of thallium was measured by both the Brookhaven whole-body counter and the Donner whole-body scanner, with excellent agreement. The effective whole-body half-time of thallium-201 is about 57 hr. Concentration of activity was seen in the heart, kidneys, large bowel, and thyroid. The whole-body radiation dose is 0.21 rads/mCi.

Thallium-201 for medical use. I.

Thallium-201 merits evaluation for myocardial visualization, kidney studies, and tumor diagnosis because of its physical and biologic properties. A method is described for preparation of this radiopharmaceutical for human use. A critical evaluation of 201Tl and other radiopharmaceuticals for myocardial visualization is given.

Airway compression by a right aortic arch in the absence of a vascular ring.

This case describes the diagnosis and successful management of an unusual form of respiratory distress in an infant with tetralogy of Fallot. Severe compression of the airway resulted from a large right aortic arch in the absence of a vascular ring.

Investigation of 125I as an isotopic source for mammography.

An isotopic radiation source 125I was investigated for use in soft tissue radiaography, with particular attention to possible use in mammography for mass screening. Film sensitivities, exposure rates, absorbed doeses, contrast and resolution were determined, and compared to conventional x-ray units. It was found that contrast and resolution were comparable to 30 kVp x-rays (W anode) but that surface absorbed dose was reduced by a factor of two with 125I. These results experimentally verified the advantage to be obtained from monoenergetic radiations, which had been predicted from theoretical considerations by others. Duration of exposure was estimated to be between 4 and 12 sec with a 40 Ci source. The 60-day half life of 125I may necessitate its use in conjunction with an image intensification system or electron radiographic techniques, in order to preclude source replacement at inconveniently short intervals.

Phosphorylation of uterine smooth muscle myosin permits actin-activation.

Myosin was purified from ovine uterine smooth muscle. The 20,000 dalton myosin light chain was phosphorylated to varying degrees by an endogenous Ca2+ dependent kinase. The kinase and endogenous phosphatases were then removed via column chromatography. In the absence of actin neither the size of the initial phosphate burst nor the steady state Mg2+-dependent ATPase activity were affected by phosphorylation. However, phosphorylation was required for actin to increase the Mg2+-dependent ATPase activity and for the myosin to superprecipitate with actin. Ca2+ did not affect the Mg2+-dependent ATPase activity in the presence or absence of action or the rate or extent of superprecipitation with actin once phosphorylation was obtained. These data indicate that: 1) phosphorylation of the 20,000 dalton myosin light chain controls the uterine smooth muscle actomyosin interaction, 2) in the absence of actin, phosphorylation does not affect either the ATPase of myosin or the size of the initial burst of phosphate and, 3) Ca2+ is important in controlling the light chain kinase but not the actomyosin interaction.

Contractile properties of actomyosin from human blood platelets.

Actomyosin was purified from human blood platelets and used to form threads via extrusion. A sensitive tensiometer was employed to measure isometric tension and velocity of isotonic shortening of the threads in the presence of MgATP. Using fully phosphorylated myosin, we obtained values for maximum isometric tension (Po) and maximum velocity of contraction (V max) that were similar to those reported for threads composed of skeletal muscle actomyosin. Po was found to be directly proportional to the level of phosphorylation of the 20,000-dalton myosin light chain. We also studied the effect of phosphorylation on superprecipitation of platelet actomyosin. Fully phosphorylated myosin produced rapid clearing and superprecipitation, while myosin with a low level of bound phosphate underwent rapid clearing but did not superprecipitate. We have concluded from these results that: 1) the interaction between platelet actin and myosin produces tension and motion that is similar to that produced by skeletal muscle actin and myosin and 2) phosphorylation of the 20,000-dalton myosin light chain in important in controlling the production of force by platelet actin and myosin.

Thallium-201 for myocardial imaging. Relation of thallium-201 to regional myocardial perfusion.

Following intravenous administration, the myocardial concentration of tracer thallium-201, potassium-43, and rubidium-81 were determined in mice; thallium was present in the greatest concentration in the myocardium (2.08% compared 1.25% for potassium and 1.15% for rubidium at 10 minutes). The regional myocardial distribution of thallium-201 was determined in dogs under conditions of normal flow, and total occlusion, and compared with potassium-43 (r=0.97). The regional distribution of thallium-201 was compared to microspheres under conditions of partial occlusion and reactive hyperemia (r=0.97). Thallium-201 was evaluated in a series of phantom scans, which demonstrated that the low energy X-ray of thallium was suitable for imaging. These results suggest that thallium-201 can be used for the evaluation of the distribution of regional myocardial perfusion.

Giant cell arteritis in a 20-year-old black man: a cause of intermittent calf claudication.

Giant cell arteritis in a young black man is an extremely unusual occurrence. A 20-year-old black man came for treatment of bilateral leg claudication that had been present for a 2-month period. His medical and angiographic evaluation led to an arterial biopsy that demonstrated giant cell arteritis. The patient was treated with corticosteroids and his condition has subsequently improved. Unusual variants of giant cell arteritis are discussed.

Congenital heart malformations associated with disproportionate ventricular septal thickening.

Asymmetric septal hypertrophy, or ASH, is a genetically determined myocardial disorder that is transmitted as an autosomal dominant trait. ASH is characterized by a disproportionately thickened ventricular septum that contains numerous hypertrophied, bizarrely-shaped and disorganized cardiac muscle cells. Disproportionate hypertrophy of the ventricular septum has also been observed in association with certain congenital cardiac malformations. To determine whether such congenital cardiac malformations are part of the disease spectrum of genetically determined ASH, cardiac pathologic observations were made in eight patients with disproportionate septal thickening (ventricular septal to posterobasal left ventricular free wall thickness ratios of 1.5 to 2.5) and the following three categories of associated lesions: 1) parachute deformity of the mitral valve (occurring either as an isolated lesion or with ventricular septal defect, coarctation of the aorta, supravalvular ring of the left atrium, or double outlet right ventricle); 2) complete interruption of the aortic arch; and 3) ventricular septal defect. The arrangement of cardiac muscle cells in the disproportionately thickened ventricular septum was normal in six of the eight patients; in the other two patients (one with parachute deformity of the mitral valve and one with ventricular septal defect) numerous bundles of hypertrophied cardiac muscle cells were interlaced in a disorganized fashion among more normally arranged bundles of cells. First degree relatives of six of the eight patients were studied by echocardiography and found to have normal ventricular wall thicknesses and septal-free wall ratios. It is concluded that disproportionate ventricular septal thickening may occur in patients with a variety of congenital heart malformations, but that such a finding is not necessarily a manifestation of the disease spectrum of genetically determined ASH.