Complete spontaneous regression of Merkel cell carcinoma: a review of the 10 reported cases.

BACKGROUND: Merkel cell (neuroendocrine) carcinoma (MCC) is a very aggressive primary cutaneous neoplasm occurring most often on the head and neck of the elderly. Complete spontaneous regression (CSR) of MCC was first described in 1986. Since then other cases have been reported bringing the total to 10. OBJECTIVE: To review these 10 cases and obtain long-term follow-up data, to compare them for similarities and differences. METHOD: Each original case report was extensively reviewed and authors contacted in most cases for confirmation and updated information. RESULTS: In no case did MCC recur after CSR was noted, although follow-up information in some cases was short. When CSR occurred, it was swift and dramatic with complete regression of skin and lymph node metastasis in 1-3 months. CONCLUSION: While only 10 cases of CSR is a small number, MCC is itself a rare malignancy with just over 600 reported cases. Today most cases of MCC receive aggressive combined therapy effectively precluding diagnosis of CSR. The nature of regression in these 10 cases may point toward future immunologic therapy just as similar cases of CRS in patients with melanoma have led to advances in the immunologic treatment for that malignancy.

Development of Peyronie's and Dupuytren's diseases in an individual after single episodes of trauma: a case report and review of the literature.

A case is presented in which a patient experienced the development of both Dupuytren's disease and Peyronie's disease after single episodes of sports-related trauma. These disorders and other fibromatoses are linked not only by similar pathologic features but by increased frequency of simultaneous occurrence. Some genetically predisposed individuals experience the development of the disorders after trauma or after some other factor unmasks that predisposition. A review of the literature with emphasis on the relationship between these fibromatoses and the varied nonsurgical attempts at treatment is presented.

Another case of spontaneous regression of Merkel cell (neuroendocrine) carcinoma.

BACKGROUND: Merkel cell (neuroendocrine) carcinoma (MCC) is a very aggressive primary cutaneous neoplasm most often occurring on the head and neck of the elderly. Spontaneous regression of MCC was first described in this journal in 1986. Since then, other such cases have been reported. This case represents the sixth case of spontaneous regression of MCC. OBJECTIVE: To describe to clinical course in a patient with MCC who underwent spontaneous regression of metastatic disease. METHODS: Clinical records including detailed history and frequent follow-up examination made this observation possible. RESULTS: Complete clinically evident regression of metastatic MCC was observed in this case. However, the patient received no treatment known to be effective for MCC. CONCLUSIONS: Spontaneous regression of MCC has been documented. The reason for regression is unknown. Further study of these rare cases may in the future provide more answers than questions.

Ketamine, at clinical concentrations, does not alter the function of cardiac sarcoplasmic reticulum calcium release channels.

In the absence of sympathetically mediated stimulation, ketamine depresses myocardial contractility. This results from a decrease in the availability of intracellular Ca2+ for excitation-contraction coupling. Although sites of action other than the Ca2+ release channel of sarcoplasmic reticulum have been implicated, ketamine-induced alterations in Ca2+ efflux from the sarcoplasmic reticulum remain contentious. The purpose of the present study was to identify interactions of ketamine with the calcium release channel using sarcoplasmic reticulum enriched vesicles from porcine left ventricle. Ketamine did not alter [3H]ryanodine binding at concentrations of 1 mM or less, while binding was almost completely inhibited at 10 mM. Gating and conductance of SR Ca2+ channels studied in planar bilayers was not altered by clinical concentrations of ketamine over the range of physiologic cytoplasmic free Ca2+ concentrations. Channel inactivation was observed at 10 mM ketamine, well in excess of clinical concentrations. These findings indicate that clinical concentrations of ketamine do not alter the function of the Ca2+ release channel. Alterations in intracellular Ca2+ homeostasis that result in depression of myocardial contractility must therefore result from effects at other sites along the excitation-contraction coupling pathway.

Activation of the Ca2+ release channel of cardiac sarcoplasmic reticulum by volatile anesthetics.

BACKGROUND: Depression of myocardial contractility associated with the volatile anesthetics is well established clinically and experimentally. The molecular mechanisms underlying this effect, however, have not been completely characterized. Whereas the Ca2+ release channel of cardiac sarcoplasmic reticulum (SR) has been implicated as a potential target contributing to anesthetic-induced myocardial depression, the effect of the volatile anesthetics on this protein have not been characterized at the isolated, single-channel level. The authors sought to identify changes in channel gating and conductance resulting from exposure to halothane, enflurane, and isoflurane that would contribute to the associated negative inotropy, as well as to explain the observation that isoflurane causes less contractile depression than either halothane or enflurane. METHODS: Vesicles enriched in SR were prepared from porcine left ventricular tissue. Fusion of these vesicles with artificial lipid bilayers under the experimental conditions provided single-channel recordings of the SR Ca2+ release channel. The gating properties and the conductance of these channels were determined in the presence and absence of clinical concentrations of halothane, enflurane, and isoflurane. RESULTS: Halothane (1.2 vol%) and enflurane (1.6 vol%) activated the Ca2+ release channel by increasing the open probability (fraction of time that the channel is open) without altering the channel conductance. These agents altered channel gating by increasing the duration of open events, rather than the number of open events. Isoflurane (1.4 vol%) had no effect on channel gating or conductance. Halothane caused dose-dependent channel activation (0.2-1.5 vol%), and channel activation was found to be reversible upon washout of halothane from the solutions bathing the lipid bilayer. CONCLUSIONS: Halothane and enflurane gate the Ca2+ release channel into the open state without altering the channel conductance. An increase in the duration of open events results from halothane and enflurane, but does not occur in the presence of isoflurane. Activation of the SR Ca2+ release channel would lead to loss of SR stores of Ca2+ into the cytoplasm, which is rapidly mobilized to the extracellular space. A net depletion of Ca2+ available for excitation-contraction coupling would result. The observation that isoflurane does not alter gating of this channel contributes to the understanding of the molecular mechanisms by which isoflurane depresses myocardial contractility less than halothane and enflurane.

L-thyroxine activates the intracellular Ca2+ release channel of skeletal muscle sarcoplasmic reticulum.

L-thyroxine activated the Ca2+ release channel (ryanodine receptor) of skeletal muscle. [3H]ryanodine binding was stimulated by L-thyroxine in a dose dependent manner producing a two-fold increase at 250 microM. The same concentration induced a release of approximately 40% of the 45Ca2+ passively loaded into sarcoplasmic reticulum in 100 msec. Ca2+ release channel activity monitored in planar bilayers increased in the presence of 250 microM L-thyroxine from a control open probability of 0.02 +/- 0.03 to 0.17 +/- 0.12. Thyroid hormones may directly open Ca2+ release channels of skeletal muscle, thus altering intracellular Ca2+ homeostasis.

Volatile anesthetics selectively alter [3H]ryanodine binding to skeletal and cardiac ryanodine receptors.

The effect of clinical concentrations of volatile anesthetics on ryanodine receptors of cardiac and skeletal muscle sarcoplasmic reticulum was evaluated using [3H]ryanodine binding. At 2 volume percent, halothane and enflurane stimulated binding to cardiac SR by 238% and 204%, respectively, while isoflurane had no effect. In contrast, halothane and enflurane had no effect on [3H]ryanodine binding to skeletal ryanodine receptors, while isoflurane produced a significant stimulation. These results suggest that volatile anesthetics interact in a site-specific manner with ryanodine receptors of cardiac or skeletal muscle to effect Ca2+ release-channel gating.

A kinetic model of benzoylecgonine disposition after cocaine administration in humans.

Cocaine (C) and benzoylecgonine (BZ) plasma levels and urinary excretion rate data from a series of intravenous cocaine studies were used to develop a kinetic model for C and BZ, with the main objective of characterizing BZ disposition. Kinetic analyses were made with the CONSAM 30 computer program. Under assumptions of the model, calculated parameters indicated a BZ distribution volume of 50 L, a half-time for BZ formation of 1.9 h and a BZ excretion half-time of 4.7 h. The model may eventually provide a basis for interpretation of analytical data on isolated samples of plasma or urine.

Characterization of theophylline binding to serum proteins in pregnant and nonpregnant women.

Sera from 10 subjects in the third trimester of pregnancy and from 10 nonpregnant women were studied to elucidate the mechanism underlying decreased theophylline protein binding during pregnancy. Consistent with the physiologic hypoalbuminemia of pregnancy, serum albumin concentrations averaged only 3.2 +/- 0.3 gm/dl (+/- SD) in pregnant subjects, compared with 4.4 +/- 0.3 gm/dl in control subjects (p less than 1 x 10(-6], and this was the main cause of decreased theophylline binding. Saturation binding studies indicated a single class of theophylline binding sites. Theophylline binding capacity (N) was greater in pregnant (N = 4.3 +/- 1.0) than in nonpregnant (N = 3.3 +/- 0.4) subjects, but binding affinity (ka) averaged only 227 +/- 69 (mol/L)-1 in pregnant subjects, compared with 303 +/- 44 (mol/L)-1 in control subjects (F2,17 = 4.26; p = 0.032). At a theophylline plasma concentration of 10 micrograms/ml, the combined effects of hypoalbuminemia and lowered ka would reduce theophylline binding to 31% +/- 3% in pregnant women, compared to 39% +/- 3% in nonpregnant control subjects (p less than 1 x 10(-5]. Nonesterified fatty acid concentrations were similar in both subject groups and did not contribute to the pregnancy-associated decrease in theophylline binding.

Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method.

N-Acetylprocainamide (NAPA) absorption and disposition were profiled in five patients with ventricular arrhythmias by the simultaneous intravenous administration of NAPA-13C and oral administration of a 500 mg NAPA hydrochloride tablet. NAPA distribution was modeled with a three compartment mammillary system. The central compartment volume of 14.1 +/- 2.6 L (mean +/- SD) was similar to expected intravascular space, corrected for NAPA partitioning between erythrocytes and plasma. Other compartment volumes, intercompartmental and nonrenal clearances, and the steady-state distribution volume of 1.45 +/- 0.09 L/kg were similar to normal subject values. The least-squares estimate of 1.67 for the NAPA renal clearance/creatinine clearance ratio was similar to the value of 1.68 previously reported for functionally anephric patients and showed the expected age-associated decrease. The oral NAPA dose was 78.0% +/- 11.7% absorbed and interindividual variation in NAPA absorption was correlated with fast intercompartmental clearance (r = 0.89, p = 0.045). Because fast intercompartmental clearance partly reflects splanchnic blood flow, hemodynamic changes may affect NAPA bioavailability, as has been found for procainamide.

Leukemic macrocheilitis associated with hairy-cell leukemia and the Melkersson-Rosenthal syndrome.

Specific cutaneous infiltrates in hairy-cell leukemia have distinctive histopathologic and histochemical findings. The true incidence of leukemia cutis in hairy-cell leukemia is uncertain, however, because reports often fail to document these distinctive features. A case of leukemic macrocheilitis associated with hairy-cell leukemia and the Melkersson-Rosenthal syndrome is presented. The Melkersson-Rosenthal syndrome is a clinically defined entity composed of Bell's palsy, macrocheilitis, and lingua plicata. Granulomatous cheilitis is often seen on histopathologic examination of the swollen lip tissue; in some cases, however, the findings may be nonspecific. Neoplastic macrocheilitis has not been reported in Melkersson-Rosenthal syndrome. Furthermore, leukemic macrocheilitis has not been reported in hairy-cell leukemia. A possible relationship between these entities is proposed.

Agnogenic myeloid metaplasia with polyarteritis.

The 1st known case of agnogenic myeloid metaplasia and chronic polysynovitis is described. The arthritis, although disabling and clinically inflammatory, has not been locally invasive or destructive. The synovial fluid showed a mononuclear cell response, and the serum was hypocomplementemic and yielded cryoglobulins. The observations are consistent with an immune pathogenesis.

Bachelor scurvy.

Scurvy occurred in an elderly man with fatigue, dyspnea on exertion, and extensive ecchymoses and brawny edema of the legs. Platelet count, prothrombin time, and partial thromboplastin time were normal, but serum ascorbic acid level was very low. Other signs considered to be classic and almost pathognomonic for were absent: bleeding gums, hyperkeratotic follicles, coiled hairs, and perifollicular hemorrhages. Reliance on these well-known features of scurvy may obscure or delay diagnosis of an easily cured disorder Severe scurvy is most commonly suggested by tenderness, extensive ecchymoses, and brawny edema of the lower extremities.

The effect of a low-phosphate diet on hematocrit and oxygen transport in uremic rats.

Dietary restriction of phosphate was found to prevent the development of anemia in partially nephrectomized rats. In an attempt to examine the reason for this beneficial effect, hematologic and nephrologic studies were carried out on normal and on partially nephrectomized rats fed either a normal or a low-phosphate diet. It was first found that a low-phosphate diet ameliorates the degree of renal impairment found four weeks after partial nephrectomy. Nevertheless, it did not eliminate it, and the degree of uremia actually observed should have been associated with a significant reduction in hemoglobin and red cell mass. However, it did reduce serum phosphate and red cell 2,3-diphosphoglycerate (2,3 DPG) levels and increase hemoglobin affinity for oxygen to a degree that should impair oxygen transport to the tissues. That the low phosphate actually caused tissue hypoxia with increased stimulation of the bone marrow was furthermore suggested by the observation that normal rats fed a low-phosphorous diet developed a significant increase above normal in hemoglobin concentration and red cell mass. It was concluded that the effect of a low-phosphate diet on the anemia of uremia is caused by a combination of reduced renal failure and increased tissue hypoxia.