PubMed HealthSearch

Biomedical subjects

M Manji

Publications and source records attributed to M Manji.

11 recordsLinked to original sources

Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.

OBJECTIVE: The cause of the metabolic disturbances in sepsis remains uncertain, but there is increasing evidence suggesting that haemodynamic changes are not solely responsible. We addressed the question of whether endotoxin has a significant effect on cellular oxygen metabolism, independent of confounding haemodynamic defects. DESIGN: Prospective, controlled experimental study. SETTING: University Laboratory. MODEL: Human hepatocyte cell line. METHODS: The oxygen consumption rate (OCR) was calculated from the fall in oxygen tension in a sealed cuvette containing Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measured in control cells and after 1, 6 and 24 h of endotoxin exposure. In a second series of experiments, resting and maximal OCR was measured after 6 and 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respiratory chain from ATP synthesis, thereby removing negative feedback and allowing the respiratory chain to work at maximal rate. RESULTS: Endotoxin caused a rise in resting OCR at 1 h which was significant by 6 h but had returned to control values by 24 h. Maximal OCR also increased at 6 h, however exposure to endotoxin for 24 h significantly reduced maximal OCR compared to the control cells. CONCLUSIONS: Endotoxin has complex effects on cellular energy metabolism causing an initial rise in the oxygen consumption rate and a significant limitation in oxygen consumption capacity at 24 h. These complex effects would be in keeping with the varied responses seen in patients.

Cell Line

Survival from massive intraoperative pulmonary thromboembolism during orthotopic liver transplantation.

We report a case of massive pulmonary embolism occurring at the time of graft reperfusion in a patient undergoing orthotopic liver transplantation. The clinical diagnosis of pulmonary embolus was aided by on-table echocardiography. Cardiopulmonary bypass and surgical embolectomy prevented her death. We discuss the differential diagnosis, possible aetiology of pulmonary embolism in this context and subsequent management.

Adult

Acute pancreatitis as a model of sepsis.

Severe acute pancreatitis has many similarities to sepsis syndrome and septic shock. The haemodynamic features of cardiovascular instability, reduced ejection fraction and decreased systemic vascular resistance are indistinguishable in each of these conditions. In addition there are many striking similarities in the cytokine and inflammatory mediator profiles, suggesting that the haemodynamic abnormalities may result from the same pathogenic mechanisms, albeit as a result of different inflammatory stimuli. Although septic complications of severe acute pancreatitis do arise these are usually late features and in the early phase of a severe attack there is sterile pancreatic necrosis. Evidence suggests that the important cytokines in the development of complications and multiple organ failure in severe acute pancreatitis are tumour necrosis factor-alpha, interleukin-1, interleukin-6 and interleukin-8. In addition, endotoxin and other important inflammatory mediators including platelet activating factor and phospholipase A2 are implicated in the development of complications in both severe acute pancreatitis and sepsis. Patients with severe acute pancreatitis are not an entirely homogeneous group but in terms of pathogenesis and complications of their disease they have much more in common with each other than the patients who are collected under the unifying diagnosis of 'sepsis'. The similar clinical and biochemical features between severe acute pancreatitis and sepsis make the former an excellent model for studying the pathogenesis of the sepsis syndrome.

Acute Disease

Pericardial metastasis in carcinoma of the uterine cervix.

Cardiac metastasis from gynecological malignancies is rare. Only six cases of carcinoma of the uterine cervix have been reported where the diagnosis of malignant pericardial effusion was made antemortem. The treatment of neoplastic pericardial effusion is controversial; both surgical and nonsurgical treatments are advocated. We present a patient with pericardial effusion secondary to carcinoma of the cervix and recommend subxiphoid pericardial fenestration for reliable long-term control of malignant effusion.

Female

Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide.

A multimodality regimen of four cycles of cisplatin and etoposide with concurrent locoregional radiotherapy (XRT) has been, since May 1988, the standard therapy for women with small cell carcinoma of the cervix (SCCC). Prophylactic cranial irradiation was to be used in all but primary progressors. All 11 patients (median age 47; 4 with pure SCCC and 7 with mixed histology) seen by us were treated with this regimen. Only 1 patient progressed while on treatment. The 3-year overall and failure-free survivals were 28%. Four patients remain alive in first remission; the remaining 7 died (2 from toxicity, 5 from cancer). Although not statistically significant due to the small numbers, it appeared that the chance of long-term survival depended both on the amount of the cancer as indicated by the FIGO stage and size of the primary and also the performance status. The toxicity was significant with 70% experiencing severe neutropenia and 40% being admitted for control of emesis. This regimen is only appropriate for those women in whom all of the apparent tumor can be encompassed within a radiation field and who, in addition, have a performance status of 0 or 1. For the remainder it does not offer any chance of long-term survival and its toxicity renders it antipalliative.

Adult

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Aged

Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome.

This study represents retrospective analysis of 87 patients with a carcinoid tumour of the gastrointestinal tract seen and followed in the British Columbia Cancer Agency (BCCA) from 1960 to 1986. In 49 cases, the primary site was the small bowel. The rest of the cases were distributed as follows: 11 appendix, 10 rectum, 5 stomach, and 7 undetermined. We extrapolated the Dukes' and modified Astler-Coller surgicopathological classifications used for colorectal cancer for use in our cases of carcinoid tumour of the gastrointestinal tract. A strong correlation was found, using this staging, with disease-specific survival. Other prognostic factors included histologic differentiation, the presence of macroscopic residual disease after initial surgery, and level of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Among 51 patients with surgically grossly removed disease, there was a tendency for the development of distant and distant/locoregional recurrence more often than locoregional recurrence alone. The liver was the commonest site of distant recurrence. Analysis of the effect of radiotherapy or chemotherapy on carcinoid tumour of the gastrointestinal tract proved unsuccessful because only a small portion of the patients had this treatment, and it was used mainly for palliation.

Adult

Iron depletion and anaemia: prevalence, consequences, diagnostic and therapeutic implications in a developing Pakistani population.

The prevalence of iron deficiency anaemia in Karachi, Pakistan, was examined in a group of 100 children, aged 2 to 6 years, and 200 adult females, aged 17 to 35 years. Anaemia, defined as a haemoglobin level less than 11.5 g/dl, was present in 47% of the children and 30% of the adult females. The majority of subjects had normal red cell counts and MCV, but haematocrit and MCH were below normal in one-quarter of the children and one-third of the adult females. More than half of both children and adult females had serum ferritin levels below normal. Many also had elevated iron binding capacity and reduced serum iron levels. Iron deficiency may be superimposed on folate deficiency in this population. The potentially serious consequences and higher prevalence of iron deficiency anaemia in children and women of childbearing age demand greater efforts toward diagnosis and eradication in developing countries.

Adolescent

Laboratory diagnosis of iron deficiency in a developing country, Pakistan.

In developing countries, such as Pakistan, laboratories do not routinely screen for iron deficiency unless the patient presents with symptoms of anaemia. Efforts to prevent the often serious consequences of iron depletion are hampered in developing countries by the expense and impracticality of routinely screening patients using bone marrow examination. Assays for serum iron concentrations, total iron-binding capacity or haemoglobin and examinations of blood films, although more practical, cannot detect the earliest stages of iron deficiency. Serum ferritin appears to be a sensitive, early indicator of iron deficiency and can be easily and relatively inexpensively determined using an immunoassay kit. In the present study, serum ferritin levels were determined using immunoassay and compared to blood films, serum iron levels and total iron-binding capacity values in 300 apparently healthy Pakistanis. In the early stages of iron deficiency, serum ferritin appeared to be a sensitive measure of iron depletion.

Adult