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Biomedical subjects

J M Howard

Publications and source records attributed to J M Howard.

At least 55 records · Page 3Linked to original sources

Macroscopic healing of esophagitis does not improve esophageal motility.

The purpose of the present study was to prospectively determine if healing of esophagitis as assessed by endoscopy results in improved esophageal motility. Thirty-one patients with erosive esophagitis who were randomized to receive either omeprazole 20 mg once daily or placebo completed the double-blind study. All patients underwent endoscopy and esophageal motility before treatment and at four weeks after treatment. Twenty-two healthy volunteers underwent esophageal manometry and served as normal controls. Manometric tracings were coded, randomized, and analyzed blindly. Compared to normal controls, patients with esophagitis had significantly lower LESP, decreased amplitude of peristaltic contractions, and increased occurrence of abnormal contractions. Omeprazole was superior to placebo in healing of esophagitis. However, healing of esophagitis was not associated with any improvement in esophageal motility. The manometric data suggest that the motility disturbance seen in esophagitis is not secondary to the esophagitis but rather a primary phenomenon. The lack of improvement of esophageal motility with healing may explain the high recurrence of esophagitis in clinical trials following discontinuation of omeprazole.

Double-Blind Method↗

Trace elements in the sweat of acclimatized persons.

Sweat samples were collected from the arms of 15 normal, healthy subjects while they exercised on a cycle ergometer at room temperature. Samples were analysed for copper, zinc, manganese, nickel, cadmium and aluminium by atomic absorption spectrophotometry. Mean sweat levels determined for each element were as follows: 358.1 micrograms/l for Zn, 486.8 micrograms/l for Cu, 3.10 micrograms/l for Mn and 1.91 micrograms/l, 69.9 micrograms/l and 15.0 micrograms/l for Cd, Ni and Al, respectively. It appears that substantial quantities of trace elements are excreted in the sweat of those sweating habitually. Our findings suggest that the influence of diet in replenishing the body stores of trace elements and the conservation of these elements by the kidneys may play a part in preventing the occurrence of chronic deficiency states in acclimatized persons.

Acclimatization↗

Trauma--the disease that was neglected. Progress: past and that to be.

Sir Harold Stiles has a historic spot in the annals of trauma care to which he and his military colleagues so richly contributed. For this we honour him today. Tremendous progress has been achieved during our lifetime in the field of trauma. Injury prevention has been the most important facet with progress underway in the fields of gun control, seatbelts, motorcycle and bicycle helmets, child restraint seats, airbags and particularly alcohol restraint. Overall, traffic fatalities are being reduced. Of great importance is the need for de-emphasis and deglamorization of violence by television, movie, and news media. Improved prehospital care has taken the form of professionalism of emergency medical services comparable to that in law enforcement and fire services. Improved hospital care is resulting, in part, from the widespread development of trauma and burn centres. Continued progress is needed in each field, particularly in gun control, alcohol control, overall traffic accident prevention, and in the understanding of cerebral oedema after head injury. The teaching of the principles of trauma prevention and community organization for better emergency medical response should be introduced into the Health or Civics curriculum perhaps at the 5th or 6th grade level in elementary schools. Perhaps the greatest potential for progress in the field of trauma which we have witnessed in our lifetime may prove to have been the actions of the United Nations in Korea in 1950 and Kuwait in 1991, proclaiming that 'war will no longer be tolerated as an instrument of national aggression'.

Accident Prevention↗

Red cell magnesium and glutathione peroxidase in infertile women--effects of oral supplementation with magnesium and selenium.

Six women with a history of unexplained infertility or early miscarriage and who had failed to normalize their red cell magnesium (RBC-Mg) levels after four months of oral magnesium supplementation (600 mg/day) were investigated for red cell glutathione peroxidase activity (RBC-GSH-Px) and were compared with six age-matched women with a history of unexplained infertility or miscarriage who did normalize their RBC-Mg levels on magnesium supplementation. The six non-normalizers had significantly lower (P < 0.0001) RBC-GSH-Px levels than the six normalizers. After a further two months of 200 micrograms daily oral selenium as selenomethionine and oral magnesium supplements, all six women normalized their RBC-Mg (P < 0.0001) and RBC-GSH-Px (P < 0.0001) levels. All 12 previously infertile women have produced normal healthy babies all conceiving within eight months of normalizing their RBC-Mg levels. The possible relevance of these findings to the medical treatment of infertility is discussed.

Abortion, Spontaneous↗

The disintegration of absorbable suture materials on exposure to human digestive juices: an update.

This is a comparative study of the disintegration of absorbable sutures when incubated in human gastric juice, bile, pancreatic juice, and their mixture. Plain catgut rapidly lost its strength in each of these digestive fluids. Chromic catgut was susceptible to digestion although it retained most of its strength in bile for two weeks. Synthetic absorbable sutures, polyglycolic acid or its derivatives (Dexon "S", Dexon Plus, and Maxon), maintained most of their strength for 2 weeks, disintegrating only after 5 to 8 weeks. Controls of saline or human plasma had little demonstrable effect. As a further control, silk maintained its strength under each exposure. Although catgut is widely used, the study suggests that it disintegrates too rapidly, at least under the conditions tested, to be appropriate for alimentary tract surgery, whereas the synthetic sutures maintained their integrity rather well for the 2 to 3 weeks needed for visceral wound healing. The data suggest that slowly absorbed synthetic sutures may be particularly useful in pancreatic or biliary anastomoses where a single layer is preferable and where a nonabsorbable suture offers inherent disadvantages.

Bile↗

Tissue-specific and differentiation-appropriate expression of the human involucrin gene in transgenic mice: an abnormal epidermal phenotype.

Involucrin is a precursor of the keratinocyte cornified envelope that is specifically expressed in the suprabasal layers of the epidermis and other stratifying squamous epithelia. To study involucrin gene expression and the function of involucrin, we expressed a 6 kb DNA fragment of the human involucrin gene, containing approximately 2.5 kb of upstream sequence and 0.5 kb of downstream sequence, in transgenic mice. The transgene produces a 68 kDa protein that is detected by a human involucrin-specific antibody, and is expressed in a tissue-specific and differentiation-appropriate manner (i.e., expression is confined to the suprabasal layers of the epidermis, extocervix, trachea, esophagus and conjunctiva). Soluble involucrin levels are two to four times higher in transgenic epidermal keratinocytes compared to human foreskin keratinocytes. Newborn heterozygous animals have a normal birth weight and a normal appearing epidermis and hair growth begins at 4 to 5 days of age (i.e., the same time as hair growth in non-transgenic animals). In a subpopulation of the newborn homozygous animals birth weight is reduced, the epidermis is scaly and hair growth begins late, at around 9 to 10 days of age. In addition, the hair tends to stand erect on both heterozygous and homozygous adult animals giving the appearance of diffuse alopecia. Immunofluorescent and electron microscopy localize involucrin in the hair follicle and cornified envelope, respectively. These results suggest that overexpression of involucrin may cause abnormalities in hair follicle structure/function and cornified envelope structure. These animals provide a new model for the study of cornified envelope structure and function.

Alopecia↗

MR imaging of the developing human brain. Part 1. Prenatal development.

To establish a baseline of the magnetic resonance (MR) imaging appearance of the fetal brain in early stages of development, the authors undertook a study of fixed and fresh specimens of embryos and fetuses of 6-28 weeks gestational age. Images of formalin-preserved and fresh specimens were comparable in their depiction of anatomic structures. On MR images of embryos of 6 weeks gestational age, the rhombic and cervical flexures, aqueduct of Sylvius, diencephalon, cerebellum, cerebral hemisphere, and fourth ventricle could be differentiated. The optic recess and chiasm, pituitary gland, pineal recess, third ventricle, pons, olfactory lobe, corpus striatum, insula, and parietal and temporal lobes could be distinguished as early as 11 weeks gestation. Although MR imaging is impractical as a screening tool for intrauterine abnormalities, it can demonstrate the fetus in great detail and allows a more specific evaluation of fetal anatomy. With the information provided by MR imaging, it may be possible to establish guidelines for assessment of the stage of development during intrauterine life.

Brain↗

Massive necrotizing pancreatitis in an immunosuppressed renal transplant recipient (successful therapy).

Severe pancreatitis may be associated with massive necrosis of the pancreas and/or retroperitoneal adipose tissue. Toxicity results from the dead tissue and secondary infection. A 45 year old patient, while fully immunosuppressed, developed this complication following cadaveric renal transplantation. He survived continued immunosuppression, 16 operative debridements of the retroperitoneum, and maintained a functioning renal transplant. In view of the previously reported high mortality rates from mild pancreatitis after transplantation, the current experience warrants further evaluation of the open method of treatment.

Acute Disease↗

Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study.

This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5-fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing.

Adenocarcinoma↗

Solitary true cyst of the pancreas in an adult.

A 35-yr-old woman was presented to the hospital because of nausea 20-30 min after eating, associated with weight loss. A CT scan revealed a cystic lesion in the neck of the pancreas. At operation, a 3-cm diameter cyst was excised from the pancreas. Endoscopic retrograde pancreatography (ERP) was used intraoperatively to identify the transected pancreatic duct, after which a Roux-Y pancreaticojejunostomy was performed. Histologically, the cyst proved to be unilocular and was lined with cuboidal epithelium. The natural history of this lesion is unknown as only four previous case reports of unilocular true cysts in adults have been reported in the English literature. These are reviewed.

Adult↗

Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma.

Thirty-eight patients with histologically proven pancreatic adenocarcinoma were investigated to establish the utility of serum CA 19-9 as a prognostic indicator. CA 19-9 assays were performed serially during the course of the disease. In four patients with negative Lewis blood type, the CA 19-9 levels remained essentially normal throughout the disease course. In the remaining 34 patients, (1) CA 19-9 levels were significantly lower in patients with tumor size no larger than 5 cm in diameter, and in patients with resectable tumors than in those with tumor size larger than 5 cm or with unresectable tumors (p less than 0.01). 2) CA 19-9 levels dropped sharply after resection in all 11 resectable patients, whereas no significant change was found after laparotomy without resection. (3) The average survival time in seven patients whose CA 19-9 levels returned to normal after resection was significantly longer than in those four patients with postoperative CA 19-9 levels that decreased but did not return to normal (21.9 versus 8.7 months, p less than 0.05). (4) In 6 of 11 patients who underwent resection, recurrent elevation of CA 19-9 preceded changes detectable by computed tomography or clinical examination by 2 to 9 months. (5) In 23 patients who died of pancreatic carcinoma, 15 (65%) had an obvious rise in CA 19-9 level before death. There was a correlation between the doubling time of the CA 19-9 serum level and survival time (r = 0.5, p less than 0.05). Because it can be demonstrated that the reduction of tumor burden by resection lowers serum CA 19-9 levels, serum CA 19-9 levels may be a useful indicator of whether other forms of treatment such as radiation therapy or chemotherapy also reduce the tumor burden.

Adenocarcinoma↗

Detection of occult metastases in pancreatic adenocarcinoma with anticytokeratin antibody.

Fifty-six lymph nodes excised from 11 patients with pancreatic adenocarcinoma were studied for evidence of metastasis by standard light microscopy and immunohistochemistry using an anticytokeratin monoclonal antibody. Eight of 56 nodes contained metastatic carcinoma as demonstrated by conventional techniques. By immunohistochemistry, positive-staining cells were easily identified. In 10 of 56 nodes, the positive staining was accompanied by cytologic atypia, changes consistent with malignancy. In seven additional nodes, positive-staining cells were present, but cytologic atypia was lacking. The use of immunohistochemistry facilitated recognition of malignant cells and raised questions that single-cell metastasis may be present. Positive staining for cytokeratin should prompt a close examination of cells to determine if morphologic features of malignancy are present.

Adenocarcinoma↗

Mucinous pancreatic ductal ectasia of latent malignancy: an emerging clinicopathologic entity.

The natural history of classic mucinous cystic neoplasms of the pancreas has been previously defined. In this report, an unusual variant of a pancreatic mucinous cystic neoplasm, termed "mucinous pancreatic duct ectasia of latent malignancy," is described. The lesion is characterized by massive dilatation of the main pancreatic duct and its tributaries. Histologically, the ducts are lined by epithelium, which is indistinguishable from the classic mucinous cystic neoplasms. Until the natural history of classic mucinous cystic neoplasm is better documented, resection appears to be the treatment of choice.

Female↗