Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers.

The effects of thrombopoietic stimulation on megakaryocytopoiesis, platelet production, and platelet viability and function were examined in normal volunteers randomized to receive single bolus subcutaneous injections of 3 microg/kg pegylated recombinant megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo in a 3:1 ratio. PEG-rHuMGDF transiently doubled circulating platelet counts, from 237 +/- 41 x 10(3)/microL to 522 +/- 90 x 10(3)/microL (P <.0001), peaking on day 12. Baseline and day-12 samples showed no differences in responsiveness of platelets to adenosine diphosphate or thrombin receptor agonist peptide (P >.4 in all cases); expression of platelet ligand-induced binding sites or annexin V binding sites (P >.6 in both cases); or density of platelet TPO-receptors (P >.5). Platelet counts normalized by day 28. The life span of autologous (111)In-labeled platelets increased from 205 +/- 18 hours (baseline) to 226 +/- 22 hours (P <.01) on day 8. Platelet life span decreased from 226 +/- 22 hours (day 8) to 178 +/- 53 hours (P <.05) on day 18. The theoretical basis for senescent changes in mean platelet life span was illustrated by biomathematical modeling. Platelet turnover increased from 43.9 +/- 11.9 x 10(3) platelets/microL/d (baseline) to 101 +/- 27.6 x 10(3) platelets/microL/d (P =.0009), and marrow megakaryocyte mass expanded from 37.4 +/- 18.5 fL/kg to 62 +/- 17 x 10(10) fL/kg (P =. 015). Although PEG-rHuMGDF initially increased megakaryocyte volume and ploidy, subsequently ploidy showed a transient reciprocal decrease when the platelet counts exceeded placebo values. In healthy human volunteers PEG-rHuMGDF transiently increases megakaryocytopoiesis 2-fold. Additionally, peripheral platelets expand correspondingly and exhibit normal function and viability during the ensuing 10 days. The induced perturbation in steady state thrombopoiesis resolves by 4 weeks. (Blood. 2000;95:2514-2522)

Long-term functional sequelae after paediatric burns.

Ninety-one patients with at least 5 per cent (median 10 per cent, maximum 50 per cent) total body surface area (TBSA) burns were clinically re-examined on average 17.3 yr after primary injury. The patients had sustained mostly superficial dermal scalds. The most common long-term functional sequelae were impaired tanning (n = 67; 77.7 per cent), diminished tactile sensibility (n = 50; 56.2 per cent) and increased reddening (n = 14; 15.6 per cent) either in the sun or the Finnish sauna. Five patients (6.3 per cent) had limited joint mobility and one patient experienced constrictive scars on her trunk during pregnancy. Scar appearance was significantly associated with impaired tactile sense (chi 2 = 11.87, DF = 2, p < 0.01; Spearman's R = 0.27, p = 0.03). Surprisingly, better scar appearance showed more disturbed touch sensation. The primary operative treatment (early excision and split skin grafting) was not associated with diminished sense of touch (chi 2 = 1.24, DF = 1, p = 0.27). Neither were scar appearance and poor tanning significantly associated (chi 2 = 1.63, DF = 1, p = 0.4). Only three patients suffered no functional detriments. In this series the harmful functional consequences were generally slight. The aetiological background (scalds) and the relatively small, superficially burned skin area probably explains the good late outcome. However, since nearly every burn-injured child will have some signs of the injury in adulthood, children present a constant challenge in the effort for better burn care and prevention.

The late appearance of scars after burns in childhood.

The late appearance of scars in children who had been burned, mainly scalded (n = 82, 90%) were analysed retrospectively from patient records and by clinical reassessment. All 91 patients who were re-examined had primarily sustained a burn of at least 5% of their total body surface area (TBSA). Only five patients showed no visible scars. The median interval between primary injury and re-examination was 17.3 years (range 6.4-30 years). Less than half of the patients (n = 36, 40%) had distinct scars without hypertrophy. The remaining 55 (60%) had either hypertrophic or constrictive scars. The scars were mostly located on the trunk (29%) and looked mainly hypertrophic (30.2%). The mean area of scars varied from 0.47% (on the neck) to 3.73% (on the left lower limb). There was no significant association between the appearance of the scar and any given method of treatment. The late cosmetic results were better than anticipated.

Latissimus dorsi breast reconstruction. Long term results and return of sensibility.

The long-term results of 44 patients who underwent breast reconstruction after mastectomy with latissimus dorsi musculocutaneous flaps with endoprostheses were studied. Good symmetry without a brassiere was achieved in 15 patients, slight asymmetry in 24 and poor symmetry in five (11%). Symmetry when a brassiere was worn was acceptable in all but one of the patients (43/44). A third of the patients (n = 13) had developed unacceptable (grade III or IV) capsular contraction, but 39 (89%) of the patients studied were satisfied with the long-term reconstruction. Cutaneous sensibility, measured by von Frey's test, had returned to 28 (64%) of the cutaneous skin islands, to their medial parts in particular. The flaps in patients who had received concentrated radiation or who had large prostheses remained numb. Sensation was normal in the scars of the donor areas in all but three patients. Latissimus dorsi breast reconstruction with an endoprosthesis is safe and simple. It gives a subjectively satisfactory result in nine out of 10 patients and is therefore a valuable method of reconstruction after mastectomy.

The impact of adjuvant radiotherapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy for breast cancer.

In an attempt to evaluate the impact of radiation therapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy a prospective study on 32 patients was performed. The radiation therapy significantly worsened the surgical outcome, because the irradiated patients more often had pectoral muscle stiffness making the expansion more painful and the reconstructed breast too small, hard and with insufficient ptosis to obtain a natural breast mould. These results indicate that this technique should be avoided in patients likely to receive postoperative adjuvant cytotoxic chemotherapy and radiation therapy, thus reducing the indication to a small group of patients undergoing mastectomy for widespread ductal carcinoma in situ.

Treatment of solitary plasmacytoma of the femur. A case report.

In radical tumour surgery the inevitable bone loss is considerable. If in addition the local tissues at the tumour site have been damaged by radiation therapy, massive endoprosthesis or even amputation should be considered. In cases with large bone loss, a vascularized fibular graft is one possibility to bridge the resected region. A case of a young man with a solitary plasmacytoma of the upper femoral diaphysis is presented. The lesion was reoperated 3 years after the primary diagnosis with resection of the non-ossified tumour site and reconstruction with a vascularized fibular graft.

The return of sensitivity to cold, warmth and pain from excessive heat in free microvascular flaps.

Recovery of sensitivity to cold, warmth and pain caused by excessive heat in various types of free microvascular flaps was studied psychophysically in 27 patients who had undergone such operations four months to four years earlier. A thermal stimulator based on the Peltier principle and controlled by a microprocessor was used to measure the sensitivity to temperature in the transplants. The results were compared with the measured thresholds in the opposite sites in corresponding normal body areas. The present study showed that sensitivity to cold, warmth, and pain caused by excessive heat did return to some free microvascular flaps. According to the measurements the sensation started to return after 6 months in some flaps, and all types of thermal stimuli were felt by one patient as early as 10 months after operation. The return was more pronounced in younger people and in smaller flaps. If the hands, feet, or head defects were reconstructed with a thin skin flap (posterior aspect of thigh, dorsum of foot, or subscapular) the recovery of sensitivity was verified. Sensation returned to the musculocutaneous and osteomusculocutaneous transfers if they were on the hands or the head, or if they were sutured to healthy tissue with normal sensation. The main advantage of the psychophysical sensory testing method that we used is that it gave exact numerical data that made it possible to compare results among the different patient groups and even those obtained at different clinics and laboratories.

[Reconstruction of the foot using free flaps]. / Fussrekonstruktionen mit freien Lappen.

Microvascular free-flap reconstruction of the foot was performed during a seven-year period in 25 patients to repair soft tissue loss caused mainly by traumatic injury. A scapular flap was used in fifteen cases, a dorsalis pedis in three, a radial forearm in two, a latissimus dorsi in two, and a gluteal thigh, rectus abdominis and tensor fascia lata each in one case. Two flaps were lost because of postoperative vascular complications. Soft-tissue stability was excellent or good in all of the seven patients with a successful free-flap transfer to the non-weightbearing part of the foot and in eleven of the sixteen patients with a flap on the weightbearing part of the foot. Four patients had frequent superficial ulcerations of the graft but only one flap was completely unstable. Sixteen patients had normal or near normal ability to walk. Significant gait problems in seven patients were caused by skeletal deformity of the reconstructed foot or other associated injuries of the lower limb rather than the reconstruction itself. The best fit and contour was provided by thin skin flaps such as the dorsalis pedis and radial forearm flaps while the scapular flap offered a more inconspicuous donor site and could be used to cover large defects. Sensibility of the flaps assessed by clinical methods was less than normal in all cases. Good sensibility was found in the flaps of two children, fair in six, poor or very poor in fifteen, and two flaps had no sensibility. The level of sensibility was not related to the soft-tissue stability of the flap.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of sensation in free flaps.

A clinical study of touch, pain, warm and cold stimuli and two-point discrimination was performed in 27 free flaps four months to four years after the microsurgical procedure. There were 5 free skin flaps (2 with nerve suture), 15 musculocutaneous, 4 muscle-covered with split skin grafts and 3 osteomusculocutaneous flaps transplanted to various sites on the body. The results show full or nearly full recovery of touch and pain sensation in all free skin flaps. The musculocutaneous and osteomusculocutaneous free flaps developed good sensation if firmly grown onto the healthy recipient skin with normal sensation. Muscle flaps covered with split skin grafts and all flaps surrounded by scar tissue had a clinical absence of sensation. This study and our earlier findings of the regeneration of nerves in free skin grafts, in skin flaps and in experimental free flaps, lead us to suggest that the healthy denervated skin of the free flap provides a strong neurotrophic stimulus to the cut cutaneous nerves in the edges of the recipient skin. Cutaneous nerves freely regenerate in the loose subcutaneous tissue of the flap. We therefore conclude that all free flaps with skin islands have a potential for developing sufficient protective touch and pain sensation and even some superficial sensitivity.

Replantation service in Helsinki University Central Hospital 1980-1985.

A replantation service is a routine part of medical services. The best results are obtained when the work is centralized. In Finland five university hospitals have a replantation service. In the Helsinki University Central Hospital, 94 severed parts of the upper limb were replanted/revascularized in 1980-85. The amputation injury requiring replantation was most often a thumb avulsed by the driving axle of a tractor. The patients came from all over the country, and the short time span between the initial injury and admission to hospital--2.4 hours an average in 1985--shows that transport of these patients is not a problem in Finland. The mean duration of surgery was 6.9 hours. Most of the operations took place in the late afternoon, evening or at night. 16% of the cases needed immediate reoperation because of vascular problems. Later, over 40% of the cases underwent secondary procedures. Most of the patients returned to their former employment. In long-term follow-up, however, nine out of ten patients reported that the replanted organ was intolerant to cold. Therefore, with the exception of the thumb, single finger replantation should not be a routine procedure in a cold climate such as that encountered in Finland. A replantation service requires a minimum of four surgeons qualified in plastic surgery or hand surgery. The operating theatre will be in use through the night. Nurses, physiotherapists and occupational therapists must be specially trained. The surgeon must be prepared to perform multiple reconstructive procedures, both immediately and later on.

Comparison of latissimus dorsi and rectus abdominis free flaps.

This review of 41 latissimus dorsi and 7 rectus abdominis free flaps describes the advantages and disadvantages of these two donor tissues. Flap survival was over 95%. Rectus abdominis carries the greatest area of skin of all the free flaps and makes salvaging of extremities with massive soft tissue loss possible, and it also provides the most elegant small free muscle flap. The latissimus dorsi is suitable for nearly any defect of the body except the foot and the hand because of bulkiness of the tissue and poor development of sensation, and the face because of poor colour match.

The rabbit ear pedicle flap. A new model for evaluating factors affecting the circulation in flaps.

Laser Doppler flowmetry and transcutaneous oximetry were compared regarding their speed and accuracy in detecting occlusion of the artery of an experimental rabbit ear pedicle flap. The laser Doppler flowmeter showed a significant decrease in flow and the transcutaneous oximeter showed a significant decrease in oxygen tension within one minute after occlusion of the artery. A significant increase in flow was observed within one minute, and a significant increase in oxygen tension readings was observed one minute after the artery was opened. A steady state after opening the artery was reached sooner for the laser Doppler flowmeter readings. This study suggests that laser Doppler flowmetry and transcutaneous oximetry are equally fast and accurate in detecting changes in blood flow to a pedicle graft. These methods also have equally good reproducibility. Repeated clampings within a 30 min period did not affect the measured parameters.

Postoperative active specific immunotherapy with supportive measures in patients suffering from recurrent metastasized melanoma: case reports of six patients.

The clinical results from postoperative active specific immunotherapy using autologous polymerized tumor material in six patients suffering from metastasized melanoma is reported. Correction of an alleged systemic deficiency leading to malignant cell transformation was attempted by administering certain essential trace elements, amino acids, vitamins, and a diet containing lipids, extracted from the mammalian central nervous system, after heating. Vaccinations against influenza were also given as a precaution against certain viral infections sometimes seen to precede melanoma recurrence. The clinical results with this postoperative adjuvant therapy are so encouraging that we suggest that sterile tumor tissue should be saved at operation and treated to produce insoluble particles as an option for postoperative treatment of patients suffering from metastasized melanoma. Prospective randomized studies are indicated.

Management of infected fractures of the tibia with associated soft tissue loss: experience with external fixation, bone grafting and soft tissue reconstruction using pedicle muscle flaps or microvascular composite tissue grafts.

The aim of this study was to assess the results of treatment given by a team of orthopaedic and plastic surgeons in a series of infected unhealed fractures of the tibia associated with loss of adjacent soft tissues. Twenty-five lower leg fractures, treated during a 10 year period, entered the study and were grouped according to the principles of treatment followed. In the earlier Group A (nine patients), the osteosynthesis implants were retained or changed to more stable internal fixation devices, the soft tissue defects were closed by conventional muscle or musculocutaneous flaps and bone grafting procedures were performed late in the treatment scheme. In the later Group B (16 patients) the implants were removed and the fracture stabilised by external fixation; the defects were covered with pedicle muscle flaps or with microvascular composite tissue grafts and cancellous bone grafting was performed at the same operation. Twenty-three fractures healed. One fracture developed non-union and in one patient infection necessitated below-knee amputation. The time of union after surgical reconstruction was significantly shorter in Group B (24 +/- 3 weeks) than in Group A (47 +/- 11 weeks). The results suggested that: in severe infected fractures of the tibia surgical implants used previously for fracture treatment should be removed and replaced with an external frame using firm axial compression, microvascular composite grafts seem to improve greatly the rate of healing, early bone grafting should be included in the reconstruction and late infections can be largely avoided even after extensive one-stage reconstructive procedures.

The effect of perfusion on post-operative viability in the replanted rabbit ear: measured by laser Doppler flowmetry and skin temperature.

The effect of perfusion by heparinized Ringer solution on post-operative microcirculation in rabbit ear replants was studied. One ear in each of five rabbits was replanted after perfusion with heparinized Ringer solution and these were compared with five replantations of rabbit ears without perfusion. The ears were studied post-operatively for 2 1/2 days by skin temperature monitoring and Laser Doppler Flowmetry (LDF). During the first day after replantation the perfused ears had better capillary flow, whereafter no significant differences were noted. LDF was more sensitive to changes in capillary blood flow, and this seems to make the reproducibility of LDF poor. It is, however, a suitable method for continued observation of post-operative viability.

Carcinoma of the lip. A retrospective study of 70 patients.

From 1966 to 1978, 70 patients with carcinoma of the lip were treated at the Division of Plastic Surgery, University Central Hospital, Helsinki. The lip tumour was a squamous cell carcinoma in 64 patients, and a basal cell carcinoma in 6 patients. Of these 70 patients, 24 had radiotherapy as the primary mode of therapy and 46 patients had been treated initially by surgery. The results of surgery were generally good. However, in the group of "simple wedge excision" and in patients who had had radiotherapy as the primary treatment there was a higher incidence of recurrences. In the former group the recurrences were considered to be due to a too narrow angle of excision. We recommend surgery as the primary method of treatment because of the availability of histologically accurate tumour margin assessment, the short rehabilitation period and the good functional results achieved.

Microvascular free flaps in early reconstruction of burns in the hand and forearm. Case reports.

In the reconstructive plastic surgery a free flap provides a one-stage method to achieve an optimal functional an aesthetic result. We report five acute burns or early contractions of the hand and forearm with free-flap reconstruction. In each case an attempt was made to design the flap to restore missing tissue components. We used three different musculocutaneous free flaps and two free skin flaps: a latissimus dorsi, a rectus abdominis and a rectus femoris renervated musculocutaneous flap, as well as a dorsalis pedis and a horizontal fasciocutaneous upper arm flap. In all five cases, the hand and wrist showed early restoration of function.