Search

Normalized maximal ventricular power (nPWRmax) is an index of cardiac function which measures the innate blood pumping ability, or contractility, of the left ventricle (LV), and its noninvasive assessment could prove useful in a variety of patients. nPWRmax is defined as the maximum instantaneous product of LV pressure and the rate of change of LV volume, divided by the end diastolic volume squared. We have quantified nPWRmax noninvasively in humans by pairing magnetic resonance imaging (MRI) LV volume measurements with aortic pressure estimated using radial artery tonometry and a frequency domain transfer function. In healthy volunteers undergoing cardiac MRI we have tested the sensitivity of nPWRmax to LV contractility with dobutamine and to cardiac loading with methoxamine, a vasoconstrictor. We have found that aortic pressures can be reliably estimated using a transfer function, which we generated and validated in a group of patients undergoing cardiac catheterization. Furthermore, we found that nPWRmax was unchanged by methoxamine, yet sensitive to contractility, with a 325% increase at dobutamine levels half that given during routine clinical cardiac stress tests for ischemia. In conclusion, we have shown that ventricular contractility can be assessed independent of cardiac loading in patients during routine noninvasive cardiac imaging examinations.

The purpose of our study was to evaluate the outcome, patterns of failure, and toxicity for patients with unresectable hepatocellular carcinoma (HCC) treated with radiotherapy, transcatheter arterial chemoembolization (TACE), or combined TACE and radiotherapy. Forty-two patients with unresectable HCC were treated with combined radiotherapy and TACE (TACE+RT group, 17 patients), radiotherapy alone (RT group, 9 patients), or with TACE alone (TACE group, 16 patients). Mean dose of radiation was 46.9 +/- 5.8 Gy in a daily fraction of 1.8 to 2 Gy, directed only to the cancer-involved areas of the liver. TACE was performed with a combination of Lipiodol, doxorubicin, cisplatin, and mitomycin C, followed by Gelfoam or Ivalon embolization. Tumor size was smaller in the TACE group (mean: 5.4 cm) compared with the TACE+RT group (8.6 cm) and the RT group (13.1 cm) (P = 0.0003). The median follow-up was 24 months in the TACE+RT group, 28 months in the RT group, and 23 months in the TACE group. Survival was significantly worse for patients treated with radiotherapy alone due to the selection bias of patients with more advanced disease and compromised condition in this group. In contrast, the TACE+RT and TACE groups had comparable survival (two-year rates: TACE+RT 58%, TACE 56%, P = 0.69). The local control rate for the treated tumors was similar in the TACE+RT and TACE groups (P = 0.11). The intrahepatic recurrence outside the treated tumors was common and similar between these two groups (P = 0.48). The extrahepatic progression-free survival was significantly shorter for patients in the TACE+RT group than in the TACE group (two-year rates: TACE+RT 36%, TACE 100%, P = 0.002). Seven patients died from complications of treatment. Local radiotherapy may be added to treat patients with unresectable HCC, and the control of progression of the treated tumors was promising even in patients with large hepatic tumors. Survival of patients with combined TACE and radiotherapy was similar to that with TACE as the only treatment, while a significant portion of the patients treated with radiotherapy developed extrahepatic metastasis., (Copyright 2001 Wiley-Liss, Inc.)

Circumferential defects of digit are uncommon but present a challenging problem to the clinician. The use of simple skin grafts tends to cause tendon adhesions and can limit digital range of motion. The use of local skin flaps, such as a cross-finger flap, is limited by the considerable skin loss in a defect that is circumferential in nature. Other options have included the use of reversed forearm flap or some free tissue transfer. We report a case in which the circumferential defect of an index finger, measuring 6 cm around the digit and 3 cm long, is resurfaced by the use of a free arterialized venous flap raised from the volar forearm skin., (Copyright 2001 Wiley-Liss, Inc.)

We report a case of Mycobacterium marinum infection of the hand presenting initially as triggering of the digits. We like to highlight the unusual source of the infection and difficulty of diagnosis in this case as well as the various treatment modalities.

A patient developed Candida albicans endocarditis and fungemia after undergoing aortic valve replacement with an allograft. The allograft had been found during tissue bank processing to be contaminated with C. albicans, but it was culture-negative for C. albicans after routine disinfection with an antifungal-containing antimicrobial solution. Comparison of the preimplantation and postimplantation C. albicans isolates revealed remarkable genetic similarity, but antifungal susceptibility testing showed that the postimplantation isolate was more resistant to fluconazole and amphotericin B than the preimplantation isolate, suggesting emergence of resistance after disinfection. Implantation of a contaminated heart valve allograft can occur despite disinfection during processing and can result in endocarditis in the recipient. Antimicrobial disinfection protocols that include antifungal drugs may be ineffective. Current U.S. Food and Drug Administration regulations do not require companies to specify details concerning allograft processing. Additional measures may be required to prevent tissue bank release of allografts contaminated with C. albicans or other pathogens.

Fixation of small bones in the adult and the child's hands remains a challenge. The authors present a technique of bone fixation using customized staples made intraoperatively from K-wires (0.9-1.6 mm in diameter). Their specific purpose was to provide axial alignment and rotational stability for carpal bone fixation and for epiphysiodesis in phalanges. This technique was used in 14 cases (11 adult and three paediatric). No bone shattering, implant breakage, implant loosening or infection occurred. As K-wires are quite malleable, custom sized and shaped staples which follow the bone contours could be made to give a more exact fixation. All cases had satisfactory outcomes, achieving the preoperative objectives of bony fixation. This method is safe, precise and technically easy. It is also relatively cheap and only requires simple, standard instruments.

A rare case of an epitheloid haemangioendothelioma presenting as an aggressive soft tissue mass in the wrist of an infant is presented. The management of the lesion presents particular difficulties because of its diffuse involvement of surrounding muscles, tendons and neurovascular bundle and the importance of preserving hand function. The epitheloid haemangioendothelioma rarely occurs extravascularly with less than 15 such cases reported in the literature.

We undertook a retrospective study of 82 patients with 128 diaphyseal fractures of the forearm who had been operated at our institution for their initial injury and subsequently had implant removal when the fractures had healed. The majority of the patients (97.5%) had no major complications after the removal of implants but 2 patients sustained a re-fracture of the same bone within 6 months after plate removal. Both patients had suffered from open fracture at the initial injury and sustained re-fracture in the original fracture site after implant removal. These fractures were both treated conservatively in a cast and united without further problems. Another 20 patients (24.4%) had minor complications ranging from mild superficial wound infection to nerve injury.

It is well documented that retained foreign bodies can be associated with delayed abscess formation in the body. We report an unusual case of a large bomb shrapnel in the wrist of a 64-year-old Chinese woman which was retained for 52 years, causing gross wrist destruction and delayed abscess formation. An open drainage of the wrist abscess was done and the shrapnel was removed. A secondary closure was subsequently done but the patient refused another procedure for a formal wrist arthrodesis.

We performed 10 digital replantations under local anaesthesia. Nine were single digit replantations and one case had a digital replantation together with another digit revascularisation. Criteria for patient selection for the local anaesthetic procedure included healthy young individuals, solitary hand injury, ability to understand the procedure and a stable emotional makeup. A combination of 10 ml of lidocaine 1% and 10 ml of bupivacaine 0.5% was used for volar metacarpal block and a dorsal ring block to the base of the digit. The patient was simultaneously sedated with 10 mg diazepam intramuscularly. Standard intraoperative monitoring of blood pressure, continuous electrocardiogram and pulse oximeter were carried out. The average duration of surgery was 3 hours. There was complete pain relief intraoperatively and good postoperative sensory block for an additional 7 to 15 hours. The technical execution of microsurgery was not compromised. All replantations were successful with no complication encountered from the use of local anaesthesia.

We report our results using University of Wisconsin (UW) cold storage solution in two cases of major replantation of the upper extremity. We employed a technique of a complete vascular washout with 1000 ml UW solution at 4 degrees Celsius at 120 cm hydrostatic pressure into the artery via a size 18 cannula. The ischaemic time of the amputated limbs were 7 hours and 11 1/4 hours respectively. No fasciotomy was performed upon revascularisation and minimal swelling was observed postoperatively. No post-ischaemic syndrome was encountered following the replantation surgery. With a follow-up of 10 and 16 months respectively, muscle and nerve viability were observed with sensory recovery and motor reinnervation. There was absence of muscle contracture and at subsequent surgical procedures, healthy musculature was present in the replanted limbs. These two clinical cases suggest that the UW solution has a role in extending the duration of tissue preservation and improving the quality of the tissues preserved.

In a retrospective study of 84 primary cadaver donor orthotopic liver transplants (OLTs), we investigated the damaging effect of preformed donor-specific antibodies by a standard T-cell warm crossmatch test (TWXM) and a more sensitive flow cytometry crossmatch test (FCXM). The incidence of a positive crossmatch was 12% (10/84) by TWXM and 24% (20/84) by FCXM, respectively. The incidence of 1-month graft failure was 30% (3/10) for patients with a positive TWXM, compared with 23% (17/74) for a negative TWXM. The deleterious effect was more pronounced when the patients were examined by FCXM. Nine of 20 (45%) FCXM-positive recipients lost their grafts within 1 month (p = 0.01) and 8 of those 9 failures occurred within 2 weeks posttransplant. A comparison of graft survival rates at 6 months demonstrated that FCXM-positive patients had a 25% lower survival rate (p = 0.01) than those with a negative FCXM. The positive rate of FCXM was 4 times higher in sensitized patients (PRA 11-100). However, 9 patients in the non-sensitized group (PRA 0-10) had a positive FCXM, and 5 of 9 patients had graft failure within 1 month, suggesting that even a low level of antibodies or non-complement fixing antibodies may have a very damaging effect. This study shows that preformed donor-specific antibodies do have a deleterious effect on allografts. Although the effect is not necessarily expressed as hyperacute rejection, the antibody response is capable of damaging the allografted organs within 1 month. Consideration should be given to crossmatching OLT patients in order to avoid transplantation over a positive crossmatch.

The unusually high 88% one-year cadaver kidney graft survival rate in patients with IgA nephropathy (IgAN) prompted us to investigate the influence of IgA anti-HLA class I antibodies on subsequent graft survival. We found that patients with various original diseases with IgA antibodies to the HLA molecule had high 91% one-year graft survival compared with 58% one-year survival for those who did not have preformed IgA antibodies against the HLA molecule prior to transplantation (P < 0.0005). The IgA antibodies were detected by reaction with class I HLA molecules isolated by capture with monoclonal antibody and detected with an enzyme-linked immunosorbent assay. In contrast, IgG antibodies to the HLA molecule resulted in a lower one-year graft survival rate (74%) than in those patients without IgG antibodies (87%) (p = 0.08). IgA antibodies to the HLA molecule, when present, tended to react at a high frequency on a random lymphocyte panel. These findings suggest that sensitization resulting in IgA anti-HLA antibodies may counteract the deleterious effect of an IgG antibody response in clinical kidney transplantation.

Granular cell tumour is a rare tumour of undetermined origin. Fewer than 1000 cases have been reported and less than 40 cases of malignant forms of this tumour have been described in the literature. We report a single case of the malignant form of granular cell tumour in the lower limb and review the literature regarding the possible origin of this tumour. Presently, wide surgical excision is the only modality of treatment for this lesion.

The infrequent occurrence of right colon diverticulitis in the developed West has led to a controversy in the management of this disease. In Singapore, we continued to avoid colectomy whenever possible because this disease is usually nonprogressive. We reviewed 68 patients treated by conservative surgery to evaluate the effectiveness of this treatment policy. Almost 70 percent of our patients were below 40 years of age, and the clinical presentation was indistinguishable from acute appendicitis. Diverticulectomy was done only for inflamed and perforated diverticula (25 cases), while the nonperforated diverticulum was left alone (40 cases). The inflammation invariably responded to antibiotic therapy. Only three patients had colonic resection since a malignant neoplasm could not be excluded. There were no adverse sequelae over a mean follow-up period of three and one-half years, except for one patient who had recurrent attacks of right colon diverticulitis necessitating colectomy. With this policy of management we encountered no mortality, and morbidity was acceptable.

Figure 9 summarizes the morphogenetic process of feather and hair. Hair of feathers are formed from a layer of homogeneously distributed mesenchymal cells. The mesenchymal cells start to condense to form foci in response to some unidentified induction signal (Fig. 9B). Several adhesion molecules, including L-CAM, N-CAM, integrin, tenascin, as well as proteoglycan, are involved. These adhesion molecules appear to have different roles in this process, because perturbation with specific antibodies leads to different aborted patterns. Hair or feather follicles then form following cell proliferation and epithelial invagination (Fig. 9C). The dermal papilla is enriched with N-CAM and tenascin, whereas the feather collar (equivalent of hair matrix) is enriched with L-CAM and PDGF receptor. Epithelial cells in the feather collar receive a signal from the dermal papilla and are able to continue to divide. Several growth factors, such as PDGF and EGF, may be involved. As epithelial cells are pushed upwards, they differentiate and keratinize in a cylindrical structure into hair. In feather, another morphogenetic event takes place to form the branched structure. The epithelial cylinder of the feather shaft invaginates to form rows of cells that die to become space and create the secondary branch or barbs (Fig. 9D). N-CAM is enriched in the cells destined to die and appears to form the border of cell groups within which the "death signal" is transmitted. In some, but not all, feathers the same process is repeated, in a way analogous to fractal formation, to form the tertiary branches or the barbules (Fig. 9E). Thus, in each step of the morphogenesis of feather and hair, different adhesion molecules are expressed and are involved in different functions: induction, mesenchymal condensation, epithelial folding, and cell death, depending on different scenarios. We have just begun to elucidate these molecular events.

We examined the binding and functional activities of monoclonal antibodies (mAbs) reactive with different structural elements of Escherichia coli and Salmonella minnesota LPS. O-side chain-reactive mAbs were highly specific for homologous, smooth LPS, bound avidly to intact bacteria, mediated complement-dependent bactericidal and/or opsonic activity, and protected against live, homologous IP challenges in mice. Core- and lipid A-specific mAbs, on the other hand, were more cross-reactive, although this cross-reactivity was severely restricted by the relative inaccessibility of epitopes in the core/lipid A region. This was reflected in the general inability of these mAbs to react with isolated smooth LPS or wild type bacteria, or to mediate bactericidal or opsonic functions. No LPS-reactive mAbs, regardless of molecular specificity, was able to block LPS- or lipid A-induced TNF production by RAW 264.7 macrophages, thus raising doubts concerning the putative endotoxin-neutralizing properties of mAbs reactive with the core/lipid A complex. Bacterial lipopolysaccharides (LPS) exhibit a complex identity. They represent an essential structural element of the outer membrane of all Gramnegative bacteria (7); they are toxins (5); they mediate a variety of immunomodulatory activities; and they are important bacterial surface antigens (2). In general, LPS macromolecules consist of three genetically, biochemically, and antigenetically distinct regions or domains: the O-side chain, core oligosaccharide, and lipid A moiety (15). Of these three regions, the O-side chain is the most phylogenetically diverse. It also represents the most antigenetically exposed element on isolated or cell-associated, native LPS. The core and lipid A structures, in contrast, are relatively conserved among different bacteria and are less accessible to antibody attack by virtue of overlying sugars contained in the O-side chain or outer core (8). In this study, we investigated selected functional activities of monoclonal antibodies (mAbs) specific for different epitopes within the three major structural domains of Escherichia coli and Salmonella minnesota LPS. The possible endotoxin-neutralizing and antibacterial properties of these mAbs were our particular focus.

A cytotoxic mouse monoclonal antibody (CALL2) was produced against a cultured T acute lymphocytic leukaemia (T ALL) cell line 8402. Ascites fluid containing the antibody was cytotoxic to a titre of up to 1:100 000 against 4 of 6 cultured T ALL cell lines and against leukaemia cells from 7 of 8 T ALL patients and 1 of 5 T chronic lymphatic leukaemia patients. The antibody did not react with normal peripheral-blood T and B lymphocytes, monocytes, granulocytes, spleen cells, thymocytes, platelets, and other acute and chronic leukaemia cells. The CALL2 antibody did not react with bone marrow stem cells of the myeloid series (CFU-C). This antibody may be useful for passive immunotherapy trials since it does not react with normal cells and is highly cytotoxic to T ALL cells.