Search

Ultrashort pulse propagation in high gain optical fiber amplifiers with normal dispersion is studied by self-similarity analysis of the nonlinear Schrödinger equation with gain. An exact asymptotic solution is found, corresponding to a linearly chirped parabolic pulse which propagates self-similarly subject to simple scaling rules. The solution has been confirmed by numerical simulations and experiments studying propagation in a Yb-doped fiber amplifier. Additional experiments show that the pulses remain parabolic after propagation through standard single mode fiber with normal dispersion.

Polarization domain-wall (PDW) trains have been generated at a repetition rate of 0.6 THz in an ultralow-birefringence spun optical fiber and measured by use of an adapted frequency-resolved optical gating technique. Characterization of the intensity and the phase of the PDW train shows complete switching between adjacent domains of counterrotating circular polarizations and directly confirms predictions based on numerical simulations of the incoherently coupled nonlinear Schrödinger equations.

The intensity and the phase of ultrashort pulses from a self-mode-locked Ti:sapphire laser operating in the vicinity of zero group-delay dispersion (GDD) have been completely characterized by the technique of frequency-resolved optical gating (FROG). For small values of negative GDD, the appearance of a dispersive wave in the pulse spectrum is manifested in the measured FROG trace, and pulse retrieval directly shows its association with a broad leading-edge pedestal. For positive GDD, we confirm previous experimental observations of picosecond pulses with large positive chirp and report a new operating regime in which the output pulses are of picosecond duration but are intensity modulated at 20 THz. The physical origin of this modulation is discussed by analogy with similar effects observed during pulse propagation in optical fibers, and the experimental results are compared with a model of intracavity four-wave mixing about the cavity zero GDD wavelength.

Cross-phase modulation in optical fibers has been used for complete characterization of ultrashort pulses by a modified frequency-resolved optical gating (FROG) measurement technique. This technique has been used for characterization of picosecond pulses at 1.5mum with energy as low as 24 pJ, and the results are in excellent agreement with second-harmonic generation (SHG)-FROG characterization. The use of an optical waveguide gives measurement sensitivity comparable with that of SHG-FROG but without any temporal ambiguity in the retrieved pulse.

The refusal of Jehovah's Witnesses with leukaemia to accept transfusion provides a major clinical challenge because of the myelosuppressive effects of chemotherapy. Experience in treating five such patients is described. Two patients with acute lymphoblastic leukaemia (ALL) achieved remission following chemotherapy, the first without transfusion support, the second, a minor, receiving transfusion under a court order: the first patient remains in remission 5 years later, whereas the second subsequently relapsed and died. Of three patients with acute myeloid leukaemia (AML), two received chemotherapy: one died of anaemia during induction chemotherapy whereas the second eventually consented to transfusion but died of refractory leukaemia. The third patient died of anaemia despite erythropoietin. We feel Jehovah's Witnesses should not be denied antileukaemic therapy if they fully understand the risks involved. Minimizing phlebotomy, use of antifibrinolytic agents and growth factors may make chemotherapy feasible, especially in ALL where remission may be induced with less myelosuppressive agents. The outlook for those with AML treated with conventional chemotherapy appears poor; alternative approaches to treatment should be considered in these patients.

Tests for folate and vitamin B12 deficiency are frequently requested by clinicians in many different specialties. An audit of folate assay methodology was undertaken to establish the number of tests and types of assay performed in different centres, and to analyse the indications for these investigations, with a view to advising on the most appropriate assay for use in the laboratory. A questionnaire was sent to 30 centres, 24 (80%) of which participated in the audit. The types of folate assay performed, number of requests, reference range and method of analysis differed between centres. The major specialty users of the service were general practitioners, general physicians and geriatricians. A detailed analysis of 1,259 consecutive requests for folate assays from a single representative laboratory showed a significant correlation between serum and red cell folate levels (r = 0.49, p < 0.001). However, in patients with low serum folate, there was no correlation with red cell folate in the absence of macrocytosis. The major indication for folate analysis was for haematological abnormalities but 36% of cases were for nonspecific indications. A haematologist with an interest in folate metabolism was invited to moderate the results at an audit meeting of haematologists. The consensus was that the most appropriate screening test for folate deficiency is the serum assay, which can be combined easily with vitamin B12 assay.

The technique of frequency-resolved optical gating is used to characterize the intensity and the phase of picosecond pulses after propagation through 700 m of fiber at close to the zero-dispersion wavelength. Using the frequency-resolved optical gating technique, we directly measure the severe temporal distortion resulting from the interplay between self-phase modulation and higher-order dispersion in this regime. The measured intensity and phase of the pulses after propagation are found to be in good agreement with the predictions of numerical simulations with the nonlinear Schrödinger equation.

Delayed haemolytic transfusion reactions (DHTRs) are seen more frequently in patients with sickle cell disease (SCD) than in other groups of patients, and are characterised by a positive direct antiglobulin test and the appearance of previously undetected red blood cell (RBC) alloantibodies in the patient's serum. Recently a syndrome of post-transfusion hyperhaemolysis has been described in children with SCD, characterised by destruction of both autologous and transfused RBCs with negative serological findings: continuation of RBC transfusion exacerbated haemolysis further. We describe a case of life-threatening post-transfusion hyperhaemolysis in an adult patient with SCD in whom severe anaemia necessitated further RBC transfusion, which was successfully performed in conjunction with intravenous immunoglobulin. This approach may be useful in the management of post-transfusion hyperhaemolysis in SCD as well as in the management of severe DHTRs.

The spectral and temporal characteristics of approximately 10-fs pulses from a self-mode-locked Ti:sapphire laser were found to exhibit large deviations from the predictions of current theories of mode locking. A simple model that takes into account coherent coupling between the circulating pulse and the gain medium gives results in good agreement with experimental observations.

We report evidence for soliton formation in a Ti:sapphire-laser-pumped femtosecond optical parametric oscillator. Appropriate conditions of dispersion are discussed, and temporal and spectral measurements of the output pulses are presented. Quantitative agreement with existing theory is implied.

The experimentally measured timing jitter of a self-mode-locked Ti:sapphire laser is compared with the theoretically predicted quantum limit. Timing jitter figures of 150 fs (100-500 Hz) and 80 fs (500-5000 Hz), which approach the quantum limit, have been achieved by use of an improved cavity phase-locking technique.

Patients with polycythaemia and normal controls have been studied to establish and subsequently test non-conventional criteria for the diagnosis of primary polycythaemia (primary proliferative polycythaemia, polycythaemia vera) as compared with conventional Polycythaemia Vera Study Group (PVSG) assessment. One criterion was erythroid colony formation from peripheral blood in a serum-free system, assayed alone and with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha interferon (alpha-IFN) (Dudley et al. 1990). The remaining criteria were non-culture associated and comprised platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), serum erythropoietin and clinical evidence of ischaemic vascular disease. The combination of culture associated and non-culture associated variables, by use of a simple additive scoring system, gave no false positive and only 6% false negative results in distinguishing primary polycythaemia from other polycythaemias and normal controls in those (34 patients Group A) used in its derivation. Testing the scoring system in a newly presenting group (25 patients Group B) was highly satisfactory with no false positives and only a few false negative results (14%). Use of these non-conventional criteria should allow more confident diagnosis of primary polycythaemia, where conventional clinical and laboratory assessment is inconclusive.

Forty adult subjects were studied with the aim of establishing positive diagnostic criteria in primary proliferative polycythaemia (polycythaemia vera, PPP). These comprised 14 patients with PPP, eight secondary polycythaemia (SP), five idiopathic erythrocytosis, and 13 normal subjects, classified under standard criteria following comprehensive investigation for causes of SP. Erythroid colony formation from peripheral blood in a serum-free system was assayed with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha-interferon (alpha-IFN). The differential sensitivity of primitive and mature progenitors (BFU-E) was assessed by counting the number of clusters ('sub-colonies') comprising each erythroid burst. 'Endogenous' erythroid colonies were found in both PPP (56%) and controls (17%). In Epo containing cultures, the mean number of clusters per burst was lower in PPP than controls, and the percentage of small (less than or equal to 8 clusters) bursts was higher. In PPP primitive BFU-E demonstrated greater dependence on IL3 than controls, and mature BFU-E greater inhibition by alpha-IFN. These findings suggest an abnormal response to several growth factors, rather than dysfunction of a single growth factor receptor. Regression analysis of these data defined a discriminant of high diagnostic sensitivity and specificity. This discriminant accurately predicted diagnosis in a further nine polycythaemic patients.

Sixty-six adults were studied with the aim of establishing positive diagnostic criteria for myeloproliferative disease. Erythroid colony formation from peripheral blood progenitors was assayed in a serum-free culture system with the addition of recombinant human growth factors. Endogenous colonies were more frequent in myeloproliferative disease than controls. The mean number of clusters per erythroid burst (BFU-e) in cultures with erythropoietin only was lower in primary proliferative polycythemia (polycythemia vera, PPP) than controls. In PPP, primitive BFU-e demonstrated greater dependence on interleukin 3 than controls, and mature BFU-e more susceptibility to inhibition by alpha-interferon. The findings indicate an abnormal response to several different cellular messengers in PPP, and permit an effective diagnostic discrimination from non-clonal polycythemias.

Splenic volume was measured by visual assessment of planar images of the spleen, and also by single photon emission computerised tomography (SPECT) using 99mtechnetium tin colloid, in a group of 33 patients with primary thrombocythaemia (PT) or reactive thrombocytosis. Volumes greater than 337 cm3 correlated strongly though not absolutely with PT, all patients with volumes greater than this figure being in the PT group. Simple visual assessment of planar images by an experienced observer matched measured splenic volumes very closely.

The formation of erythropoietic colonies from the peripheral blood of normal subjects, patients with primary proliferative polycythaemia (PPP) and primary thrombocythaemia (PT) was studied, using a chemically defined serum-free (S-) medium. Colony formation was markedly more prominent in the presence of burst-promoting activity (BPA) and erythropoietin (Ep) than with medium alone (P less than 0.001). In cultures using medium alone, significantly more PPP patients formed colonies than the control group (P less than 0.05). In the PT group this difference did not achieve statistical significance, but the mean BFU-E yield was significantly greater than in controls (P less than 0.05). In a separate series of experiments, parallel cultures in serum-containing (S+) and serum-free (S-) systems, in the presence of BPA and Ep did not show any significant difference in colony yield. The growth of 'endogenous' colonies in cultures with serum-free medium alone could be due to a peculiar sensitivity of erythropoietic progenitors to growth factors other than Ep.

Forty new patients with elevated platelet counts (greater than 600 x 10(9)/l) and without palpable splenomegaly were assigned to diagnostic groups defined by essentially conventional criteria after 3 months follow up: Proliferative (17), reactive (17) or unclassified (six). Mean platelet volume (MPV), platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), unstimulated BFU-E derived colony formation from peripheral blood, spleen scan and clinical ischaemia were assessed at the outset, with a view to defining diagnostic criteria for distinguishing primary thrombocythaemia from reactive thrombocytosis. All except the first variable were significantly associated with diagnostic group (P less than 0.05). A simple scoring system was devised: enlarged spleen on scan, or presence of BFU-E, each scored 2; elevated PDW (greater than 2 SD from mean), elevated ATP:ADP (greater than 4 SD from mean) or presence of clinical ischaemia, each scored 1. Score totals greater than or equal to 3 predicted primary thrombocythaemia, and totals less than 3 suggested reactive thrombocytosis (predictive value 89%). The system correctly predicted diagnosis in four out of four (probably six out of six) patients whose diagnosis was not apparent initially, and thus whose results were not used in constructing the scoring system. Exclusion of BFU-E from the system resulted in only one incorrect prediction in this group.