Biomedical subjects
Publications and source records attributed to M Maher.
A systematic psychiatric evaluation of 21 subjects with intraabdominal malignancy (pancreatic or gastric carcinoma) was performed. Depression was frequently associated with and often the presenting symptom complex of patients with carcinoma of the pancreas. This finding was not observed in patients with gastric carcinoma. Clinical and theoretical implications of these findings are discussed.
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Anti-idiotypic antibodies (Ab2) raised during the course of monoclonal antibody (MAb) therapy against anti-colorectal carcinoma (CRC) MAb CO17-1A were characterized in 142 patients with carcinomas of the colon, rectum or pancreas. Ab2 comprised between 21 and 80% of the total human anti-mouse IgG antibodies in various patients, and up to 42 micrograms of Ab2 were isolated per ml serum. In one patient significant levels of Ab2 could be detected for greater than 770 days. Between 20 and 70% of Ab2 in various patients bound to the combining site of MAb CO17-1A and may therefore bear the internal image of the 17-1A tumor antigen. Furthermore, Ab2 isolated from different patients showed considerable cross-reactivities. A beneficial role of the Ab2 responses in the cancer patients who improved clinically following MAb immunotherapy is discussed in light of induction by Ab2 of anti-anti-idiotypic antibodies (Ab3) with tumor-binding activities.
In our clinical experience combining wide excision and intraoperative radiotherapy (IORT), five patients have developed clinical signs of lumbosacral or sciatic neuropathy within 9 months of receiving IORT to a dose of 20-25 Gy. Three patients showed recovery of nerve function over several months while two patients have shown no recovery and have near complete loss of extremity function. In an attempt to investigate this clinical observation further, the lumbosacral plexus and sciatic nerve of American foxhounds were surgically exposed and received a single dose of IORT ranging from 20-75 Gy. An approximate linear relationship between radiation dose and time to onset of hind limb paresis is found with 19 of 21 irradiated dogs showing clinical signs of nerve injury within an interval of 1-19 months. No recovery of nerve function is seen in these dogs. Histological study of the irradiated nerves demonstrates a loss of nerve fibers, particularly those of the large myelinated type without evidence of vascular occlusion or thrombosis. These studies suggest that peripheral nerve may be a dose-limiting normal tissue in clinical studies of IORT.
Oxygen derived free radicals and peroxides result from many antitumor treatments, including radiation and anthracyclines. Doxorubicin cardiotoxicity is thought to result from free radical induced lipid peroxidation. The heart has less active detoxification enzymes than does the liver and depends on selenium dependent glutathione peroxidase (GSH-PX) for this function. We did a sequential prospective trial in patients with totally controlled parenteral diets to examine the activity of red blood cell GSH-PX in patients with and without malignant disease. Decreased GSH-PX activity was found in 54% of the patients on parenteral nutrition and was more common in the older of these patients and in those with the greatest weight loss. In the absence of selenium supplementation, the RBC GSH-PX activity declines steadily, but with supplementation this was prevented or reversed. Because selenium deficiency can manifest as a cardiomyopathy, we measured the enzyme activity in the hearts of five patients who had died. The cardiac enzyme activity correlated strongly with the RBC levels. Significantly decreased GSH-PX has been shown in animals to be associated with changes in other enzymes critical both to activation and detoxification of carcinogens as well as antitumor drugs. Abnormality of selenium status might be a previously unsuspected contributor to interpatient variation in drug effects.
Twenty-seven otherwise healthy patients with localized sarcoma were examined to determine if glucose intolerance can be detected before the appearance of clinical signs of cachexia. No patient had lost weight or demonstrated severe malnutrition. Fasting plasma samples for glucose, insulin, glucagon, and free fatty acids (FFA) were obtained, and a standard intravenous glucose tolerance test performed. Glucose disappearance rate (K) was calculated between 5 and 60 minutes. K levels were compared to those of normal controls and to those of patients with more extensive cancer (statistics obtained from the literature). Levels for K were compared to tumor volume measurements following surgery. Fasting glucose, insulin, and glucagon levels were normal. Fasting FFA levels were slightly elevated. K levels for sarcoma patients were significantly lower than in control patients (P = 0.04), and higher than in patients with advanced cancer (P less than 0.0001). The subset of patients who weighed less than the ideal had a significantly lower K level than did the rest of the sarcoma population. K levels correlated inversely with tumor volume (r = -0.34; P = 0.04). These data indicate that mild glucose intolerance (reduction in clearance of a glucose load) occurs early in untreated sarcoma patients, is most prevalent in patients who maintain less than the ideal weight, correlates with tumor burden, and occurs before other signs of cachexia appear.
To determine the nutritional effects of aggressive combined modality cancer therapy, 35 consecutive patients undergoing surgery, radiation therapy, and adjuvant chemotherapy for soft tissue sarcomas of the head, neck, and trunk were prospectively studied. Changes in body weight, total protein, albumin, total lymphocyte count, and creatinine/height ratio were studied. Significant weight loss occurred with surgery, radiation therapy, and doxorubicin/cyclophosphamide, but not methotrexate, chemotherapy. Total protein and albumin did not change significantly with any of the individual therapies. On long-term follow-up (mean 27 months), patients who survived free of sarcoma showed little nutritional morbidity. Patients with progressive sarcoma, however, showed decreases of 9% in body weight (NS), 11% in total protein (p less than 0.01), 17% in serum albumin (p less than 0.05), and 64% in total lymphocyte count (p less than 0.02). These data indicate that aggressive combined modality cancer therapy can have significant acute nutritional effects. Long-term nutritional morbidity, however, is minimal in patients without recurrent disease. In contrast, patients with recurrent disease show severe nutritional deficits which seem more a consequence of the progressive disease than of the aggressive therapy.
While deficiences of trace metals and essential fatty acids are rare in humans fed orally, the widespread use of total parenteral nutrition (TPN) has increased the likelihood of encountering these deficiences. A 14-year-old boy, with total villous atrophy of the small intestine, suffered from severe malnutrition and was placed on a conventional TPN regimen. Although not immediately recognized, he rapidly developed deficiencies of zinc, copper and essential fatty acids. Careful monitoring of the course of the illness and the responses to sequential treatments with zinc, lipid, and copper given intravenously allowed examination of the effects of the deficiencies on skin, intestine, liver, and hemopoietic systems and helped to establish normal requirements for the metals. The progress of the illness suggested that patients with intestinal malabsorption may be especially at risk of developing some of these lesser known complications of TPN.
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This study evaluated the toxicity resulting from combined therapy using carboplatin and radiotherapy in 22 patients with locally advanced (stage III and IV) head and neck cancer. Carboplatin was given after radiotherapy during the first 5 consecutive days of a 16-fraction course of radiotherapy delivered in a total of 22 days. To find the acceptable toxic dose of carboplatin, the patients were treated in groups of 3 patients each. The first group received 50 mg/m2 carboplatin and the dose was increased by 10 mg/m2 in each subsequent group. Unacceptable toxicity (severe mucositis, nausea and vomiting, and/or myelosuppression) was encountered at a carboplatin dose of 80 mg/m2. A further 10 patients were then treated at a dose of 70 mg/m2. At this dose toxicity was acceptable. Although the group of 22 patients is too small for response and survival data to be meaningful, 10 complete responses were seen and median survival is in excess of 67 weeks.
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This article describes a 22 year experience of a general surgical unit in the treatment of infantile hypertrophic pyloric stenosis (IHPS). The hospital course of 229 IHPS patients is reviewed. The male:female ratio was 3.6:1, median age 6 weeks (range 2-26 weeks) with a positive family history in 8.3%. The diagnosis of IHPS was established clinically by palpation of a "pyloric tumour" during a pre operative test meal/clinical examination in 92.6%; in the remainder, the diagnosis was made radiologically. Ramstedt's pyloromyotomy was performed within 5 days of admission in 74% of patients and within 10 days of admission in 89%. The median post-operative hospital stay was 10 days (range 3-60 days). Wound morbidity occurred in 10.0% wound infection (7.3%) and wound dehiscence (2.6%). However, wound morbidity was reduced in the second half of the series, partly by greater utililisation of non-absorbable suture in place of chromic catgut for wound closure. Mucosal penetration was suspected in 14.8% of cases. Repeat pyloromyotomy was necessary in 1.3%. One baby died (0.4%)- this was in the early part of the series and was directly attributable to fluid and electrolyte disorder. We conclude that Ramstedt's pyloromyotomy for infantile hypertrophic pyloric stenosis can be performed with acceptable morbidity and minimal mortality in a general surgical unit.
Ninety-three consecutive treadmill exercise stress test were performed for the assessment of peripheral vascular function. Thirty-one were for atypical claudication-like symptoms including pain on standing, relief on sitting and back pain. Pedal pulses were palpable in 24 patients. Twenty-five patients (81%) had a negative stress test, suggesting a non-vascular aetiology and this finding was subsequently confirmed in 24 of the 25. The final diagnoses were spinal stenosis 13, [CT = 3, myelogram = 5, neurosurgeon opinion = 4, MRI = 1], myositis 2, restless leg syndrome 2 and osteoarthritis 7. Four patients had symptoms due to a combination of peripheral occlusive arterial disease and spinal stenosis; the latter was considered the predominant disorder in all four. Of the original 31 patients with atypical symptoms, spinal stenosis was present in 13 (42%). Atypia- in the common syndrome of intermittent claudication should alert the surgeon to the possibility of spinal canal disorders. Further investigation may identify significant pathology spinal stenosis in particular.