Iodine deficiency disorder (IDD) presenting as hypothyroidism with a large pericardial effusion

Iodine deficiency in Zimbabwe is common, but resultant hypothyroidism is said to be rare. A case of goitrous hypothyroidism with a large pericardia effusion is presented.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.     

Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

Strain-specific alterations in consumption of a palatable diet following repeated stressor exposure.

Exposure to acute inescapable shock caused reductions in the consumption of a highly palatable diet. The magnitude and duration of the reduction varied across strains of mice. With repeated exposure to footshock, consumption of the diet returned to baseline levels, although alterations of weight appeared to be more persistent. The course of the adaptation varied across strains of mice; however, the rate of adaptation was unrelated to the extent of the alterations of consumption induced by the acute stressor. When mice were exposed to a series of different stressors, the adaptation progressed less readily, and reductions of diet consumption were apparent in strains that had not shown such an effect following acute stressor application or when repeatedly exposed to a single type of stressor. Data were discussed with respect to the mechanisms that might be operative in subserving stressor-induced anhedonia.     

Characterisation of passively transferred antigen arthritis induced by methylated bovine serum albumin in the rat: effect of FK 506 on arthritis development.

The conditions necessary for the passive transfer of antigen arthritis induced by methylated bovine serum albumin (mBSA) in the rat have been studied. Spleen cells from immunised rats were not capable of transferring disease unless they were first activated in culture with mBSA or concanavalin A. Cells from sham-immunised animals could not be activated to transfer the arthritis. The immunosuppressant drug FK 506 could inhibit the development of the arthritis when present during the activation period in culture or when dosed to the recipients of activated cells.     

Providing psychological support for patients after critical illness.

The majority of patients have little or no memory of their stay in ICU or remember only pain, suctioning or lack of sleep. Dreams and nightmares while in the intensive care unit (ICU) and after discharge home have also been reported. The few studies investigating the longer-term psychological problems of critical illness point to a picture of social isolation with patients avoiding company and showing less affection to their partners. Our own experience, running a special outpatient clinic and following up patients by post, showed a picture of depression, anxiety, irritability and social isolation. This led to the setting up of an ICU staff-led support group for patients recovering from critical illness. This article outlines the possible problems and pitfalls of setting up and running a support group for patients recovering from critical illness. The type of patients suitable to attend such a group is examined. Two case histories give an illustration of the type of problems ICU patients experience during their recovery and how an informal support group can help. In addition to possible benefits to the patients, support groups can also give ICU staff a chance to understand the process of recovery from critical illness and to examine the effects on patients of their own practice. However, they must also have enough insight to know when a patient needs professional help; for example, a patient displaying symptoms of post-traumatic stress disorder should be referred, with their agreement, to a clinical psychologist.     

Long-term sequelae of Palmar-Plantar erythrodysaesthesia syndrome secondary to 5-fluorouracil therapy.

Palmar-Plantar erythrodyasesthesia syndrome has been reported as a temporary complication of 5-fluorouracil therapy consisting of a debilitating erythema and tenderness of the skin of hands and feet. The syndrome has previously been observed to respond rapidly to either temporary cessation of chemotherapy or pyridoxine with little residual disability. We report a case which was characterized by persistent morbidity necessitating prolonged discontinuation of treatment.     

Testicular descent. III. The neonatal mouse gubernaculum shows rhythmic contraction in organ culture in response to calcitonin gene-related peptide.

The effects of calcitonin gene-related peptide (CGRP) and CGRP 8-37 on the neonatal mouse gubernaculum were examined in organ culture, with the aim of seeing whether CGRP has a direct effect on the gubernaculum. A total of 440 gubernacula were studied. Two hundred and fifty gubernacula were treated with CGRP in concentrations ranging from 0-714 nM/liter. With increasing doses of CGRP the percentage of gubernacula showing vigorous contraction increased from 18-50%. The total percentage of gubernacula showing any form of contraction increased from 76-96%. One hundred and fifty gubernacula were exposed to the CGRP analog CGRP 8-37. Increasing concentrations of CGRP 8-37 from 179-714 nM/liter decreased the rate of vigorous contraction from 18-4%. The percentage of gubernacula showing any degree of contraction decreased from 76-14%. Forty gubernacula removed from testicular feminization (TFM) mice were exposed to varying concentrations of CGRP. In the absence of exogenous CGRP no contractility was observed. By contrast, in the presence of CGRP the gubernacula showed vigorous contractility increasing from 38-90%. The total number of gubernacula showing contraction increased from 75-100%. These studies demonstrated that the neonatal mouse gubernaculum exhibits a high level of endogenous contractility, which can be enhanced in a dose responsive manner with exogenous CGRP. CGRP 8-37 caused a dose responsive inhibition. The androgen-insensitive gubernaculum from the TFM mouse showed no endogenous contraction, but on exposure to CGRP showed an enhanced rate of contractility. These results are consistent with the hypothesis that androgens may control gubernacular migration indirectly via release of CGRP from the genitofemoral nerve in the inguinoscrotal region. The failure of gubernacular motility in vitro and migration in vivo in the TFM mouse may indicate lack of CGRP release from the genitofemoral nerve.