Biomedical subjects
Publications and source records attributed to J H Shaw.
This review examines current knowledge regarding the metabolic responses to trauma and sepsis. The factors which may mediate the responses are discussed and the potential value of pharmacological or nutritional manipulation is reviewed.
We have performed paired isotopic studies in four patients undergoing resection of early colorectal cancer and four having removal of parathyroid adenomas. Kinetic measurements of protein and glucose metabolism were made before resection and at home 10 weeks after surgery. During convalescence there were major changes in both groups in glucose metabolism and the hormonal milieu despite no alterations in protein kinetics or metabolic rate. In particular, the rate of glucose production doubled from (mean +/- s.e.m.) 14.8 +/- 1.3 to 28.1 +/- 2.5 mumol kg-1 min-1 (P less than 0.01), the percentage of available glucose undergoing oxidation decreased from 35.5 +/- 3.9 to 21.5 +/- 2.9 per cent (P less than 0.05) and the percentage of glucose undergoing recycling to lactate increased from 20.1 +/- 10.0 to 52.9 +/- 2.3 per cent (P less than 0.05). During convalescence the basal plasma insulin concentration was significantly higher (P less than 0.05) and there was a proportionately smaller response to glucose infusion. The convalescent state was also associated with an elevation in serum cortisol from 291 +/- 54 to 496 +/- 75 nmol litre-1 (P less than 0.05). The values for resting energy expenditure were not significantly different from the predicted energy expenditure in either the preoperative or the convalescent groups. We conclude that (a) there is a marked increase in both glucose production and glucose recycling to lactate in convalescence from clean uncomplicated surgery, and this is associated with a decrease in the percentage of glucose uptake oxidised; (b) a relative hyperinsulinaemia is seen in convalescent patients and is associated with decreased responsiveness to a glucose load; (c) the plasma cortisol level is significantly elevated after 10 weeks of convalescence; and (d) convalescent patients do not have elevated rates of protein catabolism or energy expenditure.
Twenty-four patients who underwent resection of giant spleen (spleen weight greater than 1.5 kg) have been reviewed to determine the difficulties and benefits of the procedure and, in particular, whether the use of adrenaline injection into the splenic artery could safely reduce technical difficulty. Although morbidity was higher in patients with giant spleens compared with those undergoing resection of smaller spleens the incidence of serious complications was small, and there were no operative or in-hospital deaths. In addition, virtually all patients benefited either on the basis of minimized haematological defect, or palliation of symptoms. Further, the injection of 1 ml of 1:10,000 adrenaline into the splenic artery before splenic mobilization reduced the splenic volume by approximately 40 per cent on average, and resulted in improved exposure, thereby facilitating the procedure.
Three cases of histologically confirmed neutropenic enterocolitis, each presenting as an acute abdomen in patients with leukaemia are presented. All three patients presented with fever and abdominal pain within 14 days of completing a course of chemotherapy. Signs of peritonitis localized to the right iliac fossa developed in each patient, in spite of aggressive antibiotic therapy and bowel rest. All three patients were found to have non-viable caecum at laparotomy and were treated by right hemicolectomy. Primary ileocolic anastomosis was performed in one patient, who recovered following a stormy postoperative course owing to sepsis. Two patients underwent formation of an ileostomy with distal mucous fistula and each recovered with minimal postoperative complications; secondary anastomosis was performed electively in both cases. The difficulty in diagnosing neutropenic enterocolitis preoperatively is discussed and the place of non-operative management is reviewed but we recommend surgical intervention as a means of ensuring removal of a localized septic focus until marrow regeneration occurs.
We have reviewed the local experience of 15 cases of thyroid lymphoma with a view to documenting the epidemiology, presentation, management and prognostic factors governing outcome for this rare condition. All the patients were European despite the fact that 15 per cent of the local population is either Maori or Polynesian. The average age at presentation was 62 years and 13 of the 15 patients were women. The duration of symptoms was short: on average 9 months. Where feasible a definitive resection of the lesion was performed but this could only be performed in six of the 15 cases. The commonest histological type was non-Hodgkin's lymphoma which accounted for 14 of the 15 cases with the large cell variant being the most common (five cases). The mean period of follow-up was 3.3 years: only eight patients were alive and well at that time. The prognostic factors that influenced outcome were: (1) the histology of the lesion - large cell lymphoma carried a bad outlook; (2) whether the lesion could be totally resected or not - five out of six patients undergoing total resection remain alive and well; (3) the presence of pre-existing Hashimoto's thyroiditis was a favourable prognostic factor as only one patient without underlying Hashimoto's disease or positive antithyroid antibodies was alive at the end of the study; (4) male sex may also be an unfavourable prognostic factor as both men in the study died of disease 0.3 and 5 years after diagnosis.
This review examines the infectious consequences of elective and emergency splenectomy, highlighting the importance of infection with Streptococcus pneumoniae. The influence of splenectomy on the immune system is discussed and the efficacy of vaccines in preventing postsplenectomy sepsis is reviewed. The value of alternative methods of preventing postsplenectomy sepsis is considered.
A series of isotopic infusions were performed in 43 severely ill patients suffering from blunt trauma (mean injury severity score of 31). The patient data have been compared with data obtained from 32 normal volunteers, and in addition the metabolic response of the trauma patient to total nutritional support (TPN) has been assessed. The rate of VO2 was elevated in the trauma patients compared with that of the volunteers (160 mumol/kg/minute vs. 103 mumol/kg/minute). Glucose production was significantly increased in the patients compared with the volunteers (21 +/- 2 mumol/kg/minute vs. 14 +/- 1 mumol/kg/minute), but the trauma patients had an impaired capacity to directly oxidize plasma glucose. The percentage of glucose uptake oxidized in the volunteers was 36 +/- 2%, and the percentage of glucose uptake recycled was 10 +/- 1%. By contrast, in the trauma patients, 23 +/- 4% of the glucose uptake was directly oxidized, and 29 +/- 11% was recycled. The rate of glycerol turnover in the trauma patients (5.3 +/- 0.3 mumol/kg/minute) was significantly elevated compared with the volunteer value (2.2 +/- 0.1 mumol/kg/minute), and the basal rate of fat oxidation was twice as high in the patients as in the volunteers (2 mg/kg/minute vs. 1 mg/kg/minute). The rate of whole body protein catabolism was significantly higher in the patients (5.8 +/- 0.7 g/kg/day vs. 4.3 +/- 0.3 g/kg/day), and as a result, the rate of net protein catabolism was significantly elevated in the patients. The response to TPN (amino acids and a 50:50 mixture of glucose and fat) included an increase in the percentage of glucose uptake oxidized (up to 45 +/- 12%), a decrease in the oxidation of fat (up to 0.8 mg/kg/minute), and a significant increase in whole body protein synthesis (up to 6.1 +/- 1.1 g/kg/day) so that the rate of net protein loss was minimized but not prevented. (The rate of net protein catabolism during TPN was 1.3 +/- 0.5 g/kg/day.) There was no correlation between the injury severity score (ISS) and the degree of metabolic abnormality. The rate of NPC in the patients with ISS less than 20 was higher than in the volunteers (ISS = 0), but the values for NPC in patients with ISS 21-40, and ISS greater than 40 were virtually identical to the corresponding values in patients with ISS less than 20. It is concluded from these studies that: 1) Trauma patients have a high rate of VO2.(ABSTRACT TRUNCATED AT 250 WORDS)
This report comprises a retrospective review of the clinical data on 157 patients seen in the Auckland area having a diagnosis of cancer of the tongue, floor of the mouth, inferior alveolus, or buccal mucosa (retromolar area, vestibule of the mouth, and cheek mucosa) during 1970-86. One hundred patients were male, 95% were European, 85% were cigarette smokers, and 58% had a history of high alcohol intake. All primary tumours were squamous cell carcinomas, 50% were located in the tongue, 27% in the floor of the mouth, and 11.5% each in the buccal mucosa and inferior alveolus. The majority (60%) of patients with tongue cancer were clinically stage I at presentation while other intra-oral tumours were evenly distributed between stages I and IV. Surgical resection of the primary intra-oral lesion produced local control in 90% of stage I tumours, but this fell to below 70% in stage II-IV tumours. Most patients (82%) who recurred locally had positive or 'close' margins, and this rate of local tumour recurrence as a consequence of narrow margins did not decrease with the addition of adjuvant radiotherapy. Of those patients with stage I disease who received only treatment of the primary lesion, 20% later developed regional nodal disease which was controlled in more than half by neck dissection, but control was achieved only in 11% of patients treated with radiation. The presence of regional disease at presentation was associated with a poor prognosis. It is concluded that local control of inferior oral cavity tumours can be achieved if resection is accomplished with clear margins.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoid tumours in Auckland diagnosed during 1976-87 have been reviewed retrospectively. Eighty-three patients with carcinoid tumours were seen during this time (56 appendiceal, 11 small bowel, two colorectal, 10 pulmonary and four other). Three patients had carcinoid syndrome. The most common presentation for appendiceal carcinoid was acute appendicitis. The most common presentations for pulmonary lesions were incidental findings on chest X-ray, recurrent chest infection or haemoptysis, while bowel lesions presented with abdominal pain or rectal bleeding. Following resection, 53 of 56 appendiceal patients were alive and well (two died from other causes) and 10 of 10 pulmonary carcinoids were alive and well. In contrast, both patients with colorectal carcinoid died from their disease within 1 year, and, of the patients with small bowel carcinoid, one died of the disease and more than half of the remainder are alive with metastatic spread and symptoms at the time of study. The most important prognostic variables governing outcome were anatomical site of the primary lesion and the state of the histological margins following resection.
The case-notes of 30 patients presenting with primary gastric lymphoma in the Auckland area during 1969-87 have been reviewed. The mean age of the study group was 62 years, and 16 were female and 14 were male. There were 22 European, one Maori and seven Polynesian patients. The most common presenting symptom was abdominal pain and five patients presented acutely with gastrointestinal haemorrhage. The lesions occurred more frequently in the distal stomach and half were polypoid and half were ulcerating. They tended to be of substantial size at presentation, with seven being greater than 10 cm in diameter. Nine lesions were confined to the stomach, 12 involved the surrounding lymph nodes and eight were invading adjacent organs. Twenty-three patients underwent partial or total gastrectomy. Four of these received postoperative radiotherapy, and adjuvant chemotherapy was administered to 13. Chemotherapy, or combination chemo- and radiotherapy were used as the primary treatment in seven patients. Following surgical treatment, 18 patients remained alive and well. Five of the seven patients treated nonsurgically were dead of disease at the time of study and the other two remained alive with persisting disease. The following factors were found to affect prognosis adversely: weight loss of greater than 5 kg, tumour invasion of adjacent organs, and non-surgical primary treatment. Involvement of the lymph nodes draining the stomach did not appear to worsen the outlook, and there was little correlation between lesion size and prognosis.
Of 148 elective splenectomies performed in Auckland during 1979-87, 48 were performed as therapy for immune thrombocytopenic purpura (ITP). In all cases medical therapy had either failed to maintain their platelet count (36 patients), or side-effects of medical treatment had made continuation unacceptable (12 patients). The mean age of the group was 31 years and there were 15 males and 33 females. Thirty-four of 48 patients (71%) had a favourable response to splenectomy: platelet count was maintained above 150 x 10(9)/l and medical therapy was no longer required. There was no operative or inhospital mortality. Seven patients experienced postoperative complications (mainly infections) of which none were life-threatening. There was no difference in response between males and females (67% and 73% response rate, respectively), and the response rates of Europeans and non-Europeans were similar (71% and 69%, respectively). By contrast, the average age of the responders [29 years) was almost 10 years younger than the non-responders (38 years). It is concluded that the use of splenectomy as therapy for patients with ITP, who have either failed to respond to medical management or for various reasons cannot tolerate the complications associated with steroid therapy, is a safe procedure which in the present series was associated with no operative mortality and an acceptably low rate of morbidity. Younger ITP patients (less than 30 years) have a better chance of responding favourably to splenectomy than do older patients (greater than 40 years).
We have reviewed the clinical and pathological records of 4 patients presenting for treatment of parathyroid cyst in Auckland between 1970 and 1987. The mean age of the patients was 60.5 years and 3 patients presented with symptomatic hyperparathyroidism (2 male and 1 female patient) and 1 female patient presented with a neck mass and tracheal compression. All cysts were unilocular and filled with clear fluid (mean cyst diameter was 1.5 cm and mean cyst weight was 5.55 g). Four out of the 5 cysts were located in the inferior neck. Of the three patients with hyperparathyroidism, 2 patients had associated parathyroid adenoma (1 patient having bilateral cystic adenomas) and 1 patient had hyperplasia of the remaining glandular tissue. We conclude that parathyroid cyst is an uncommon clinical problem of uncertain aetiology affecting middle aged and elderly patients.
The authors used isotopic infusions of 6-3H-glucose, U-14C-glucose, and 14C-urea and calorimetry to investigate energy expenditure and metabolic profiles in 19 patients with hematologic malignancy. The average age of these patients was 62 years. Eleven patients had either leukemia or myeloproliferative disorders (LEMP). The rest had lymphoma (LYMPH). The Resting Energy Expenditure (REE) in the LYMPH patients was 1015 +/- 115 kcal/24 hr. This value in the LEMP group was significantly elevated at 2083 +/- 270 kcal/24 hr (P less than 0.025) despite similar weights and ages between the two groups. Net Protein Catabolism (NPC) in the LYMPH group was 82 +/- 29 mg/kg.hr. In contrast the value in the LEMP group was more than doubled at 174 +/- 30 mg/kg.hr (P less than 0.05). Glucose production in the LYMPH group was 14.1 +/- 2.7 mumol/kg.min, and the percent of glucose uptake oxidized in the LYMPH group was 37% +/- 9%. In contrast, glucose production in the LEMP group was significantly elevated (P less than 0.025) at 41.0 +/- 8.1 mumol/kg.min, and the percent of glucose uptake oxidized was significantly depressed (P less than 0.05) at 20% +/- 4% compared with the value in the LYMPH group. Glucose recycling in the LYMPH group was 9.0% +/- 6%. In the LEMP group the rate of recycling was significantly elevated at 60.3% +/- 4.8% (P less than 0.005). The percent suppression of endogenous glucose turnover during glucose infusion in the LYMPH group was 96% +/- 4%. The value for the LEMP patients was significantly less at 30.2% +/- 5% (P less than 0.0005). The serum cortisol concentration in the LYMPH patients was 285 +/- 74 nmol/l. The value in the LEMP patients was significantly higher (P less than 0.005) at 579 +/- 22 nmol/l. The authors concluded that hematologic malignancy is not a homogeneous group when evaluated metabolically. Lymphoma patients are similar metabolically to normal volunteers, but LEMP patients form a distinct group with major abnormalities in both glucose and protein kinetics and energy expenditure.
We have reviewed the records of 105 patients with the diagnosis of soft tissue sarcoma seen in the Auckland region between January 1974 and December 1984. The mean age at diagnosis was 54 years and the average duration of symptoms prior to specialist assessment was 8 months. By the time of presentation 27% of patients had metastatic disease. Forty-six patients underwent biopsy-type procedures and of these only one patient was alive and apparently disease free at one year. Three were alive with disease at an average of 2.2 years, 29 of the 46 had died of their sarcoma at one year and five of the 46 died of other causes. Fifty nine patients had definitive reactions performed and 26 of were alive with disease at an average of 2.2 years, 29 of the 46 had died of their sarcoma at one year and five of the 46 died of these were alive and disease free at two years. Six were alive with recurrent disease and 15 had died of sarcoma 1.9 years after presentation. In terms of site of the primary, patients with limb sarcomas fared better than those with retroperitoneal lesions, whereas sarcomas in other locations had survival figures in between these two groups. Soft tissue sarcomas consitute an aggressive and unforgiving type of cancer, and to entertain any realistic chance of cure complete resection of the lesion must be achieved. However, the patients presented to specialist attention at a relatively late stage of their disease, and the chances of survival are dependent both on the site of the primary lesion and on whether or not definitive surgery and adjuvant therapy is employed.
We have retrospectively reviewed the charts of 34 acral melanoma patients (melanoma arising from the volar skin of the hands, feet or a subungual site) seen in the Auckland area between 1970 and 1985. These 34 patients constituted 3.5 per cent of the total number of patients (972) reviewed over this period. Six of the thirty-four patients were either Polynesian or Maori. There were 19 men and 15 women, and the mean age of the group was 59 years. The primary lesion arose from the plantar or palmar skin in 25 patients and 9 patients had subungual lesions. All lesions but one were pigmented. Most patients with plantar or palmar lesions presented with clinical stage 1, Clark's level 4 disease, while those with subungual lesions presented most commonly with stage 2, Clark's level 5 disease. Treatment was wide local resection for plantar and palmar lesions and amputation for subungual lesions. Regional lymph node dissection was performed in 10 patients with positive nodes at presentation and in 6 patients who developed metachronous nodal disease. Patients were followed for between 1 and 16 years, and 18 patients died in this period, 15 of metastatic melanoma (mean time 34 months). Subungual melanoma carried a worse prognosis than melanoma arising in palmar or plantar skin.
We performed a series of 14C[urea] infusions to assess the effect of depletion (greater than 15% decrease in body weight), stress (VO2 greater than 130 mumol.kg-1.min-1), and cancer on the basal rate of net protein catabolism (NPC) and the response of patients to total parenteral nutrition (TPN). Depleted patients had low rates of NPC (0.8 +/- 0.1 g.kg-1.d-1) compared with nondepleted patients (p less than 0.05) and during TPN anabolism was achieved (0.5 +/- 0.2 g.kg-1.d-1). Gastrointestinal (GI) cancer patients had rates of NPC similar to those of normal volunteers; during TPN, NPC approximated zero. Severely stressed (SS) nondepleted patients had high rates of NPC (2.7 +/- 0.2 g.k-1.d-1) whereas SS-depleted patients had lower (p less than 0.05) rates of NPC (1.9 +/- 0.3 g.kg-1.d-1); both groups of SS patients remained catabolic despite TPN (1.2 +/- 0.3 and 0.5 +/- 0.2 g.kg-1.d-1, respectively). In response to TPN, depleted patients become anabolic, GI cancer patients stop losing protein but do not become anabolic, and stressed patients remain catabolic and continue to loss protein.
We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS)
We have performed a series of isotopic infusions both in normal volunteers (N = 16) and in sarcoma patients (N = 7). Using the primed-constant infusion of stable or radioisotopes we have determined the rates of glucose turnover, glucose oxidation, glucose recycling, and net protein catabolism (NPC). In addition, we have measured VO2 and VCO2. The values for VCO2 and VO2 were higher in the patients than in the volunteers (mean VO2 values in volunteers and patients: 107 +/- 13 and 158 +/- 13 mumol/kg/min, respectively). The basal rate of glucose appearance in the sarcoma patients was twice the value seen in the volunteers (28.3 +/- 3.5 vs. 13.9 +/- 0.3 mumol/kg/min). Glucose infusion in the volunteers resulted in virtually total suppression of endogenous glucose production, while in the patients glucose infusion induced only a 30% suppression of endogenous glucose production (p less than 0.01). The rate of glucose clearance in the patients was approximately twice the value seen in the volunteers [5.4 +/- 1.0 vs. 2.7 +/- 0.1 mL/kg/min (p less than 0.01)]. The per cent of glucose uptake oxidized in the patients was significantly less than in the volunteers [22% vs. 36% (p less than 0.05)], and the per cent of glucose uptake that was recycled was significantly higher in the patients [55% vs. 10% (p less than 0.01)]. In addition, the basal rate of net protein loss was increased twofold in the patients [3.2 +/- 0.5 vs. 1.4 +/- 0.4 g (protein)/kg/d (p less than 0.01)], and in contrast to the situation in the volunteers there was no suppression in the rate of net protein loss when the patients were infused with glucose. The basal insulin concentration and the insulin response to glucose infusion in the patients were similar to that of the volunteers, but the plasma cortisol level was similar in volunteers and in the patients (p less than 0.05). We conclude from these studies the following: (1) Sarcoma patients have significantly elevated rates of glucose production and glucose clearance, but they have an impaired capacity to directly oxidize either endogenous or infused glucose, coupled with an increased rate of glucose recycling. (2) Sarcoma patients have an elevated metabolic rate and are catabolic. In addition, in contrast with normal volunteers, glucose infusion does not result in a suppression of protein loss.