The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
The quest for improving and maintaining sexual function has been going on since time immemorial. The advent of an effective oral drug, sildenafil, has brought about unprecedented open discussion on male erectile dysfunction, and gas accelerated the pace of development of new therapies for erectile dysfunction. New knowledge in the physiology of sexual function has enabled researchers to target drug treatment at the whole network of the central nervous system and the numerous cascadic enzymatic reactions leading to relaxation of the corporal smooth muscle. One of the brightest potential applications of future molecular technology in the study of erectile dysfuction is in the utilization of gene therapy.
A clinicohistological study of acute atherosis in molar pregnancy was undertaken. Maternal decidual vessels in currettage samples of 38 histologically confirmed complete hydatidiform moles were examined histologically for acute atherosis, recognised as fibrinoid necrosis of the smooth muscle wall with a perivascular mononuclear cell infiltrate, with or without lipophages. Acute atherosis was detected in eight of 38 cases, an incidence of 18.4%. All the patients were normotensive. The significance of acute atherosis in molar pregnancy remains to be clarified.
Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN) resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.
Thirteen patients had skeletal reconstruction using vascularised fibula graft following resection of the diseased bone. Eleven patients had reconstruction of the lower limbs and two patients of the upper limbs. Clinical and radiographical evidence union were achieved with the average time of 32 weeks (earliest eight weeks). Six out of 11 patients (54%) in lower limb reconstruction started weight bearing at the average of 27 weeks. Bony union in this study is comparable with other studies using vascularised fibula graft.
The skull base attachment of the second lamella and suprabullar pneumatization are likely to be consistent landmarks if they are systematically classified. This study aimed to classify the pneumatization pattern according to the second lamella skull base attachment. A total of 202 computed tomography sides of 101 patients who underwent endoscopic sinus surgery were studied. Suprabullar pneumatization was defined as air cells present above the ethmoid bulla between the second and third lamellae. Its pattern was classified according to the air cell number and location as in the frontal cell classification. Type 0 suprabullar pneumatization was defined as no air cells between the ethmoid bulla and skull base; type 1, as a single suprabullar cell; and type 2, as multiple suprabullar cells above the ethmoid bulla. In type 3 pneumatization, the second lamella extended into the frontal sinus forming a frontal bullar cell. Type 2 was the most prevalent (40.1 %), followed by types 1, 3, and 0 (24.3, 23.3, and 12.4 %, respectively). The distance between the second lamella and anterior ethmoid artery was 8.93, 8.30, 8.50, and 11.25 mm in types 0, 1, 2, and 3 pneumatization, respectively. No patients had intraoperative injuries in the anterior ethmoid artery or lateral lamella. The second lamella skull base attachment and suprabullar pneumatization pattern could be systematically classified and be a consistent landmark to identify the frontal sinus opening.
NEW FINDINGS: What is the central question of this study? The liver regenerative process is complex and involves a sequence of signalling events, but the possible involvement of structural and haemodynamic changes in vivo during this process has never been explored. What is the main finding and its importance? Normal sinusoidal blood flow and velocity are crucial for a normal regenerative response, and delays in these haemodynamic events resulted in impaired liver regeneration in lipopolysaccharide-insensitive, C3H/HeJ mice. Toll-like receptor 4 signalling is required for restoration of normal liver architecture during the liver regenerative process. Liver regeneration is delayed in mice with a defective Toll-like receptor 4 (TLR4; C3H/HeJ mice) but is normal in TLR4 knockouts (TLR4-/- ). Here, we investigated the possible involvement of structural and haemodynamic changes in vivo in the underlying mechanism. In lipopolysaccharide-sensitive (C3H/HeN and C57BL/6) and lipopolysaccharide-insensitive (C3H/HeJ and TLR4-/- ) mice, a 70% partial hepatectomy (PH) was performed under inhalational anaesthesia. At days 3 and 7 after PH, the hepatic microcirculation was interrogated using intravital microscopy. Delayed liver regeneration was confirmed in C3H/HeJ, but not in C3H/HeN, C57BL/6 (WT) or TLR4-/- mice by liver weight-to-body-weight ratio, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells and mitotic index data. At day 3 after PH, sinusoidal red blood cell velocity increased by 100% in C3H/HeN mice, but by only 40% in C3H/HeJ mice. Estimated sinusoidal blood flow was significantly higher at day 7 after PH in C3H/HeN than in C3H/HeJ mice. The hepatic cord width was significantly larger in C3H/HeN than in C3H/HeJ mice at day 3 and it was significantly larger in TLR4-/- than in C57BL/6 WT mice at day 7 after PH. Hepatocyte nucleus density and functional sinusoidal density was significantly reduced at days 3 and 7 after PH in all mouse strains compared with their zero-time controls. Functional sinusoidal density was significantly lower in C3H/HeJ compared with C3H/HeN mice at day 7 after PH. The present study indicates that altered sinusoidal blood flow and velocity in C3H/HeJ mice may contribute to the observed delay in the regenerative response in these mice. In addition, restoration of normal liver architecture may be delayed in TLR4-/- mice.
Hypertension complicates chronic pyelonephritis. Since arterial narrowing is common in the damaged kidney, activation of the renin-angiotensin system due to renal ischaemia has been suggested as a pathogenetic mechanism. We used an antiserum to human renin and an immunoperoxidase technique to study the anatomy of renin-containing cells (RCC) in 18 kidneys removed for pyeloneophritis. We independently assessed the degree of arterial narrowing and correlated these variables with the clinical findings. There was histological evidence of hyperplasia of RCC in 5 of the 6 hypertensive patients and in 7 of the 12 non-hypertensive cases. There was no difference in the apparent number or distribution of RCC between the hypertensive and the non-hypertensive cases. Also, the degree of arterial narrowing did not correlate with either the hyperplasia of RCC or the blood pressure of the patients. Our results do not support the hypothesis that narrowing of the intrarenal arteries is important in the pathogenesis of hypertension in pyelonephritis. In our cases, the renal veins were more severely damaged than the arteries and their lumina were often obliterated by organized thrombus. We suggest that such widespread obliteration of the renal venous tree could impair blood flow and contribute to the tissue damage in the pyelonephritic kidney.
Bilateral ligation of the internal iliac artery with or without ligation of the ovarian arteries was carried out in 17 patients who had life-threatening pelvic haemorrhage; 14 were due to obstetric haemorrhage, 2 followed abdominal hysterectomy and 1 intractable haemorrhage associated with carcinoma of the cervix. The procedure was successful in arresting the haemorrhage in 13 patients but 4 needed hysterectomy in spite of the ligation; 1 patient died from disseminated intravascular coagulation following surgery and 1 had cardiac arrest due to extensive blood loss during surgery and died 12 hours later. A review of the literature, a brief description of the procedure and its indications are discussed.
Findings are reviewed of isolated Patent Ductus Arteriosus after infancy as seen in 181 patients studied at the University Hospital, Kuala Lumpur, during the period 1967 to 1975. The ages of patients ranged from nine months to 54 years. Eighty-two patients underwent cardiac catheterization. More than 50% of patients were above ten years of age; the sex ratio was 1 male: 2.93 females. Thirty-two per cent of the patients had significant effort dyspnoea or were in heart failure. The complications noted were elevated pulmonary vascular resistance, Eisenmenger syndrome, bacterial endocarditis and cardiac failure.
Tissue recovery is important in preventing tissue deterioration, which is induced by pressure and may lead to pressure ulcers (PU). Reactive hyperaemia (RH) is an indicator used to identify people at risk of PU. In this study, the effect of different recovery times on RH trend is investigated during repetitive loading. Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385-485 g, were categorised into three groups and subjected to different recovery times with three repetitive loading cycles. The first, second, and third groups were subjected to short (3 min), moderate (10 min), and prolonged (40 min) recovery, respectively, while fixed loading time and pressure (10 min and 50 mmHg, respectively). Peak hyperaemia was measured in the three cycles to determine trends associated with different recovery times. Three RH trends (increasing, decreasing, and inconsistent) were observed. As the recovery time is increased (3 min vs. 10 min vs. 40 min), the number of samples with increasing RH trend decreases (57% vs. 29% vs. 14%) and the number of samples with inconsistent RH trend increases (29% vs. 57% vs. 72%). All groups consists of one sample with decreasing RH trend (14%). Results confirm that different recovery times affect the RH trend during repetitive loading. The RH trend may be used to determine the sufficient recovery time of an individual to avoid PU development.
The association of mast cells with typical lesions of Kimura's disease was investigated by quantitative methods after immunohistochemical staining for Factor VIII-related antigen and counterstaining with toluidine blue. Formalin-fixed, paraffin-embedded, tissue sections from 9 confirmed cases of Kimura's disease were examined after staining to estimate mast cell and blood vessel densities by counting 100 random fields under oil immersion. There was a statistically significant increase of both mast cells and blood vessels in Kimura's disease (p<0.01) compared with normal skin and reactive lymph node controls. However, as far as the individual Kimura's disease lesion is concerned, there was generally no correlation between areas with mast cell increase and the degree of vascularity. Moreover, when lesions of less than 1 year's duration were compared with older lesions, there appeared to be a relative decrease in mast cells and a concomitant increase in vascularity in the latter. These results confirmed that mast cells are associated with Kimura's disease, and suggest that they may be involved in its early pathogenesis, although its possible role in angiogenesis may not be direct.
Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.
Carotid sinus hypersensitivity (CSH) is associated with syncope, unexplained falls, and drop attacks in older people but occurs asymptomatically in 35% of community-dwelling elders. We hypothesized that impaired cerebral autoregulation is associated with the conversion of asymptomatic CSH to symptomatic CSH. We therefore conducted a case-control study evaluating individuals with CSH with and without the symptoms of syncope or unexplained falls, as well as non-CSH controls, to determine whether the blood pressure and heart rate changes associated with CSH are associated with symptoms only when cerebral autoregulation is altered.
Dieulafoy's lesion is one of an unusual cause of upper gastrointestinal bleeding (U GIB). Endoscopic intervention has always been a preferred non-surgical method in treating UGIB including bleeding from Dieulafoy's lesion. Owing to recent advances in angiography, arterial embolization has become a popular alternative in non- variceal UGIB especially in cases with failed endoscopic treatment. However, managing bleeding Dieulafoy's with selective arterial embolization as the first line of treatment has not been exclusively practiced. We hereby, report a case of bleeding Dieulafoy lesion which had been primarily treated with arterial embolization.
This is a case report on an uncommon correlation between periodic lateralized epileptiform discharges (PLEDs) and white-matter lesions in cerebral lupus, and with a reduced cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). A 47-year-old woman with a long-term history of systemic lupus erythematosus (SLE) presented with a seizure followed by frontal lobe dysfunction clinically. An electroencephalogram (EEG) showed bilateral independent PLEDs in the frontal region. A magnetic resonance image of the brain showed white-matter changes in the frontal periventricular region. Cerebral angiogram did not reveal any evidence of vasculitis. A cerebral SPECT with tracer injected during the EEG showing PLEDs showed a reduction in CBF in the frontal regions. Clinical recovery was observed with intravenous immunoglobulin. This case shows that PLEDs can be seen with white-matter changes in SLE.
A 10-month-old boy was referred for tachypnea and heart murmur. An echocardiogram showed unexplained left heart dilation without evidence of an intracardiac shunt. A 64-slice computed tomographic contrast-enhanced angiography showed a large tortuous anomalous artery arising from the descending thoracic aorta and supplying the lower lobe of the left lung. The venous return into the left atrium was normal. The affected lobe had normal lung parenchyma, and its bronchial tree was connected normally with the left main bronchus. Hence, it was not a sequestrated lobe. The boy underwent surgical lobectomy of the left lower lobe and improved. Anomalous arterial supply of a lobe without sequestration of its bronchial tree is a rare pathologic entity. It also is a very rare cause of congestive heart failure in children. Computed tomographic angiography was a useful tool for evaluation of the intrathoracic anomalous vessel in this case.
We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury.
In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 15(1)-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 microL volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 microg per embryo of G2 and a light dose of 20 J cm(-2) at a fluence rate of 40 mW cm(-2) filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer.