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Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 73 records · Page 4Linked to original sources
PubMed1992

A comparison of the gastrointestinal side effects of two forms of erythromycin.

BACKGROUND: The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. METHODS: This was a multicenter, prospective, single-blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. RESULTS: There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI-related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). CONCLUSIONS: Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI-symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less.

Adult↗
PubMed1991

Mucolipidosis type IV: clinical manifestations and natural history.

The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.

Adolescent↗
PubMed1991

Taurine-conjugated bile acids act as Ca2+ ionophores.

The ionophoretic properties of several taurine-conjugated bile acids have been investigated in two experimental systems: in a two-phase bulk partitioning system and in proteoliposomes. In the former, a bile acid/Ca2+ complex was extracted into the bulk organic phase and had an experimental stoichiometry of 1.75. Extraction was specific for Ca2+ over Mg2+; Na+ and K+ did not compete with the extraction of Ca2+. In the second system, bile acids at concentrations as low as 5-100 molecules/vesicle lowered the steady-state Ca2+ gradient maintained by a reconstituted sarcoplasmic reticulum Ca(2+)-ATPase. The effect was not due to nonspecific membrane perturbation. In addition to releasing intravesicular Ca2+ in a transmembraneous process, bile acids caused partition of Ca2+/bile acid complexes into the hydrophobic core of the bilayer. In both experimental systems, the Ca2+ ionophoretic activity correlated well with the concentration and the hydrophobicity of the bile acid. Taurolithocholate was most active, with a significant effect measurable at 10 microM in either system. Since bile acid concentrations equal to those used in our experiments can occur in the blood in certain liver diseases, the results support the notion that bile acids can increase the intracellular Ca2+ concentration bypassing the regulatory systems that maintain cellular Ca2+ homeostasis.

Animals↗
PubMed1991

Gallstone formation after major abdominal surgery.

84 patients underwent multiple abdominal ultrasound examinations over a median of 36 months (range 6-140). 11 had gallstones at their first ultrasound examination, and were excluded from further analysis. Of the remaining 73 patients, 12 of 47 who underwent major abdominal surgery had gallstones within 14-36 months of operation, compared with 0 of 26 who did not undergo such surgery. The cumulative prevalence of new gallstones within 3 years of major surgery was 28%; no new gallstones were seen from 36 to up to 140 months postoperatively. By univariate and logistic regression analysis, age and major abdominal surgery were the only significant clinical determinants for the appearance of gallstones during follow-up. The findings of this retrospective study indicate that major abdominal surgery may accelerate the development of gallstones in some patients. If confirmed in a prospective study, it may be possible to define groups at high risk of gallstones after surgery and to institute prophylactic measures.

Abdomen↗
PubMed1991

Non-operative management of blunt liver injuries.

Over a 10-year period 281 patients with liver injuries following blunt abdominal trauma were seen at Westmead Hospital. A decision to treat the liver injury without an operation was made in 55 (20 per cent) of the 281 patients. Two of these 55 patients required a subsequent laparotomy, one for continued bleeding and one for a bile leak. No patient died from a missed intra-abdominal or retroperitoneal injury or from concealed haemorrhage. These patients were compared with 181 patients with liver injuries who were operated on. The two groups of patients could be distinguished in terms of their clinical status on arrival at the hospital, the magnitude of their injury and the sequelae of the injury. Non-operative management proved a safe alternative to an operation in appropriate patients, but a laparotomy to exclude unsuspected intra-abdominal injuries is associated with little significant morbidity and offers some reassurance in managing patients with multiple injuries.

Adolescent↗
PubMed1991

Urinary excretion of lithocholic acid and its conjugates by the bile duct-ligated rat.

The 3-O-glucuronide of lithocholic acid has been shown to be a potent cholestatic agent in rats. However, even after the onset of lithocholic acid glucuronide-induced cholestasis, little of the administered material was recovered in urine. To determine whether this phenomenon was related to the steroid moiety or the form of conjugation, small doses of radiolabeled lithocholic acid glucuronide, lithocholic acid, taurolithocholic acid and/or lithocholic acid sulfate were administered to rats with ligated bile ducts. Urinary excretion of isotope was followed for 24 hr and urinary metabolites of the administered compounds were identified by thin-layer chromatography. Lithocholic and taurolithocholic acids were slowly but relatively efficiently excreted in urine with 73% and 91% of the dose, respectively, recovered in urine over 24 hr. More than 80% of the label in urine from animals receiving these two compounds was in the form of taurine-conjugated beta-muricholic acid. In contrast, lithocholic acid 3-glucuronide and 3-sulfate were poorly excreted: 9% and 12% of the administered doses, respectively, were recovered in urine in 24 hr. Of the small amount of label in urine from rats given the glucuronide, 90% was identified as lithocholic and taurolithocholic acid glucuronides. When lithocholic acid sulfate was given, thin-layer chromatography of urine showed two peaks, which were tentatively identified as tauromurideoxycholic and taurolithocholic acid sulfates. More definitive identification was not possible because of the small amount of the administered dose excreted in urine in these forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Post-traumatic bile fistulae.

Bile leakage after liver injury has been reported to be a complication associated with significant mortality. In a prospective study of 306 patients with liver injuries 13 (4%) developed a bile leak. There appear to be two groups of patients, those with a major bile duct injury (three patients) and those with a more peripheral injury (ten patients). Bile leaks may present either as bile peritonitis (six patients) or as a bile leak through a drain site (seven patients). All but one bile leak closed spontaneously at a median of 33 days (range, 3-110 days). There was no mortality but patients incurred a median of four complications each (range, 1-5). This may reflect the severity of the initial injury rather than the bile leak. Respiratory failure and/or infection and sepsis were the most common complications whilst abnormalities of liver function, although common, were seldom of clinical significance.

Adolescent↗
PubMed1991

Palliation of malignant jaundice.

The great majority--perhaps 90%--of patients with malignant jaundice can only be treated by palliative means. The best method of palliation is yet to be defined. Some groups advocate routine surgical bypass, while others hold that all cases should be managed by the insertion of stents, either endoscopically or percutaneously. Recovery from surgery consumes a significant portion of residual lifespan, while stents produce long-term morbidity from stent blockage and cholangitis. The present study used a convenient and simple method to quantify the quality of life that follows surgical bypass and stent insertion. Six patients were followed for at least 6 months after open bypass, and nine after stent insertion. Four patients in each group were still alive at 12 months. The study suggests that there is no significant difference in the quality of life obtained by either method at 6 months, but that there is a clear-cut advantage in having surgical bypass by 12 months. The study points to the need to evolve better stents, to improve stent management and to define criteria which will identify patients who are likely to survive more than 6 months.

Aged↗
PubMed1991

Impact of the CUSA and operative ultrasound on hepatic resection.

New technologies have been developed for liver surgery, and, like all new technologies, they have a glamour which makes them seem desirable. There is an understanding abroad that they make liver surgery easier and open up the field to those without special training. But there is no proof that the new devices are in any way cost-effective, and certainly no proof that liver surgery has become safer since their advent. Fifty consecutive elective liver resections have been studied, almost half performed with the aid of the ultrasonic dissector and aspirator and diagnostic intraoperative ultrasound. There was no mortality in the whole group, but a 24% morbidity. Operative diagnostic ultrasound was thought to allow more precise planning of surgery. Its use was not associated with any increase in operative time, nor was there any increase in postoperative morbidity. The ultrasonic dissector and aspirator improved technique, reflected in a lower blood loss for each case, in fewer transfusions required, in a shorter postoperative hospital stay and in an ability to achieve these benefits in older patients. Neither device could be said to offer an entree to instant liver surgery. The use of the two devices apparently offered savings measured by a fall in the median postoperative hospital stay of 4.5 days, by a saving of 700 mls in median blood requirement and by a fall in transfusion rate from 64% to 9%.

Adolescent↗
PubMed1991

Hepatic dystychoma: a five year experience.

In 5 years, 64 solid hepatic lesions have been referred for diagnosis and management which have been found unexpectedly on organ imaging in well patients. We have called this lesion a "dystychoma". Patients have undergone a two phase investigation programme which allows a diagnosis without admission to hospital in about 50% of cases. About three quarters of patients (47/64) have had non-neoplastic lesions, and about half (33/64) have had haemangiomas. About one patient in four (17/64) has had a neoplasm, and the neoplasm has been malignant in about one in six (11/64) of all patients. We stress the need to pursue the diagnosis in these patients. There were no reliable clinical, biochemical or imaging characteristics which individually distinguished benign from malignant lesions. Age over 55 years, an enlarged liver or a palpable liver mass and a raised serum alkaline phosphatase were all significantly more frequent with malignant tumours. The risk of malignancy rose with the number of risk factors, and all patients with all three risk factors had malignant tumours. Only 11 of the 64 patients were judged to have benefited by significant increase in quality or quantity of life as a result of what was frequently inappropriate organ imaging. There is no strong argument for replacing history taking and physical examination by CT scanning, ultrasound examination or other organ imaging.

Adolescent↗
PubMed1991

Hepatic metabolism of short-chain bile acids. Inversion of the 3-hydroxyl group of isoetianic acid (3 beta-hydroxy-5 beta-androstane-17 beta-carboxylic acid) by the adult rat.

The stereospecificity of mechanisms for hepatic transport of short-chain bile acids has been examined by following the hepatic metabolism and biliary secretion of 3 beta-hydroxy-5 beta-androstane-17 beta-carboxylic acid (isoetianic acid) administered in two different labeled forms to rats prepared with an external biliary fistula. While 93% of the administered [2,2,4,4-3H]isoetianic acid was recovered in bile after 20 h, only 18% of a similar dose of [3 alpha-3H]isoetianic acid was secreted in bile over the same time period. The recovered radioactivity of the latter compound was mainly associated with bile water. With the [2,2,4,4-3H]isoetianic acid, the bulk of the biliary isotope was determined to be in the form of two glucuronide conjugates. Spectral analysis identified these metabolites as the hydroxyl-linked (major) and carboxyl-linked (minor) beta-glucuronides, not of the 3 beta-hydroxy compound administered, but of 3 alpha-hydroxy-5 beta-androstane-17 beta-carboxylic acid (etianic acid), i.e., the products of hydroxyl group inversion. It is concluded that isoetianic acid is efficiently cleared from plasma and conjugated with glucuronic acid after its epimerization to etianic acid. The prevalent, but not complete, loss of the 3-tritium atom and the retention of the 2- and 4-tritium atoms probably indicates a 3-oxo-5 beta-androstane-17 beta-carboxylic acid intermediate with partial return of the label via a limited labeled pool of reduced nicotinamide cofactor.

Androstanols↗
PubMed1991

Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation.

In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells.

Acute Disease↗
PubMed1990

Canine pancreas and kidney transplantation following total-lymphoid irradiation.

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.

Animals↗
PubMed1990

Mozart's requiem--liver transplantation in 1988.

Liver transplantation is one of the most spectacular of surgical achievements. It is a demanding and expensive procedure, requiring great surgical skill and a great depth of supporting services. Precisely because it is a procedure at the leading edge of medicine, more and more units in developed countries are pressing to be allowed to carry it out. But there are many moral and ethical problems, some of which can be usefully examined using a "Mozart model" as proposed by Starzl.

Austria↗
PubMed1990

Leber's congenital amaurosis with Duchenne's muscular dystrophy.

We studied a family with Leber's congenital amaurosis and Duchenne's muscular dystrophy. One son, the proband, was noted to be blind from shortly after birth and had absent pupillary reflexes, attenuation of retinal blood vessels and pigmentary changes of the retina. He manifested Duchenne's muscular dystrophy at 6 years of age and died of its complication--severe respiratory failure--at 21 years of age. His older brother also was blind since birth, with absent pupillary light reflexes and an extinguished electroretinogram in both eyes. The proband's younger brother with Duchenne's muscular dystrophy died following respiratory failure. Their oldest brother was apparently unaffected. Their mother and sister were proven carriers of Duchenne's muscular dystrophy and a maternal uncle and great-uncle also died from this condition. The parents were consanguineous, third generation cousins.

Adolescent↗